UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 14A

SCHEDULE 14A INFORMATION

Proxy Statement Pursuant to Section 14(a)

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505 Penobscot Dr.

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NOTICE OF 20212022 ANNUAL MEETING OF STOCKHOLDERS

TO BE HELD ON JUNE 16, 2021

PROXY STATEMENT

INFORMATION CONCERNING VOTING AND SOLICITATION

General

Your proxy is solicited on behalf of the Board of Directors (the “Board”) of Guardant Health, Inc., a Delaware corporation (as used herein, “Guardant,"” ”Guardant Health,"” “we,” “us” or “our”), for use at our 20212022 annual meeting of stockholders (the “Annual Meeting”) to be held on Wednesday, June 16, 2021,15, 2022, at 9:30 a.m. Pacific Time, virtually at www.virtualshareholdermeeting.com/GH2021www. virtualshareholdermeeting.com/GH2022, or at any continuation, postponement or adjournment thereof, for the purposes discussed in this proxy statement and in the accompanying Notice of Annual Meeting and any other business properly brought before the Annual Meeting. Proxies are solicited to give all stockholders an opportunity to vote on matters properly presented at the Annual Meeting.

Virtual Annual Meeting. The Annual Meeting will be a virtual meeting of stockholders using cutting-edge technology, conducted via live audio webcast. You are invited to attend the Annual Meeting online. We believe that a virtual meeting provides expanded stockholder access and participation, improved communications, as well as additional safeguards for health and safety related to the COVID-19 pandemic.improved communications. You will be able to attend, vote and submit your questions online during the Annual Meeting. You will not be able to attend the Annual Meeting in person. Stockholders may attend the Annual Meeting online by logging into www.virtualshareholdermeeting.com/GH2021ww. virtualshareholdermeeting.com/GH2022 using the 16-digit control number included on your Notice of Internet Availability of Proxy Materials, on your proxy card, or on the voting instruction form provided by your broker, bank or other nominee.

Notice and Access Proxy Delivery. We have elected to provide access to our proxy materials over the Internet. Accordingly, we are sending a Notice of Internet Availability of Proxy Materials (the “Notice”) to most of our stockholders of record, and paper copies of the proxy materials to certain other stockholders of record. Brokers and other nominees who hold shares on behalf of beneficial owners will be sending their own similar Notice to such beneficial owners. All stockholders will have the ability to access the proxy materials on the website referred to in the Notice or request to receive a printed set of the proxy materials. You can find instructions on how to request a printed copy by mail or electronically on the Notice and on the website referred to in the Notice, including an option to request paper copies on an ongoing basis. On or about April 29, 2021,28, 2022, we intend to make this proxy statement available on the Internet and to commence mailing of the Notice to all stockholders entitled to vote at the Annual Meeting. We intend to mail this proxy statement, together with a proxy card, to those stockholders entitled to vote at the Annual Meeting who properly request paper copies of such materials, within three business days of such request.

Important Notice Regarding the Availability of Proxy Materials for the 20212022 Annual Stockholder Meeting to be Held on June 16, 2021

Our proxy statement and 20202021 Annual Report are available at www.proxyvote.com. This website address contains: the Notice of Annual Meeting, the proxy statement and proxy card sample, and the 2020

Who Can Vote, Outstanding Shares

Record holders of our common stock as of the close of business on April 19, 2021,18, 2022, the record date for the Annual Meeting (the “Record Date”), are entitled to notice of and to vote at the Annual Meeting on all matters to be voted upon. As of the Record Date, there were 101,117,510101,919,898 shares of our common stock outstanding. On each matter presented to our stockholders for vote, the holders of common stock are entitled to one vote per share held as of the Record Date.

Voting of Shares

The method of voting by proxy differs (1) depending on whether you are viewing this proxy statement on the Internet or receiving a paper copy and (2) for shares held as a record holder and shares held in “street name.”

Record Holder. If you hold your shares of common stock as a record holder and you are viewing this proxy statement on the Internet, you may vote by submitting a proxy over the Internet by following the instructions on the website referred to in the Notice previously mailed to you. If you hold your shares of common stock as a record holder and you are reviewing a paper copy of this proxy statement, you may vote your shares by completing, dating and signing the proxy card that was included with the proxy statement and promptly returning it in the preaddressed, postage paid envelope provided to you, or by submitting a proxy over the Internet or by telephone by following the instructions on the proxy card.

Hold in Street Name. If you hold your shares of common stock in street name, which means your shares are held of record by a broker, bank or nominee, you will receive a Notice from your broker, bank or other nominee that includes instructions on how to vote your shares. Your broker, bank or nominee will allow you to deliver your voting instructions over the Internet and may also permit you to vote by telephone. In addition, you may request paper copies of the proxy statement and proxy card from your broker by following the instructions on the Notice provided by your broker.

General. The Internet and telephone voting facilities will close at 11:59 p.m. EDT on June 15, 2021.14, 2022. If you vote through the Internet, you should be aware that you may incur costs to access the Internet, such as usage charges from telephone companies or Internet service providers and that these costs must be borne by you. If you vote by Internet or telephone, then you need not return a written proxy card by mail.

Voting at the Virtual Annual Meeting. To attend and vote at the Annual Meeting you need to access the meeting via live audio webcast at www.virtualshareholdermeeting.com/GH2021GH2022 using the 16-digit control number included on your Notice, on your proxy card or on the voting instruction form. Attendance at the Annual Meeting will not, by itself, result in any vote or revocation of a prior vote. You must follow the instructions at www.virtualshareholdermeeting.
com/GH2021GH2022 to vote your shares at the Annual Meeting.

The proxy gives each of Helmy Eltoukhy, AmirAli Talasaz and John Saia discretionary authority to vote your shares in accordance with their best judgment with respect to all additional matters that might come before the Annual Meeting.

Revocation of Proxy

If your shares are held of record, you may change or revoke your proxy at any time before your proxy is voted at the Annual Meeting by taking any of the following actions:

Written notices of revocation and other communications with respect to the revocation of proxies by record holders should be addressed to:

Broker Non-Votes

Brokers, banks or other nominees who hold shares of common stock in “street name” for a beneficial owner of those shares typically have the authority to vote in their discretion on “routine” proposals when they have not received instructions on how to vote on such matter from beneficial owners. However, brokers are not allowed to exercise their voting discretion with respect to the election of directors or for the approval of matters that are considered “non-routine”“non-routine” without specific voting instructions from the beneficial owner. If you hold your shares in street name and do not provide voting instructions to your broker or other nominee on how to vote on the election of directors or other “non-routine”“non-routine” proposals, your broker cannot exercise discretion to vote you shares and your shares will be considered to be “broker non-votes” and will not be voted on such matters. Accordingly, if your broker holds your common stock in “street name,” your broker will vote your shares on the election of directors and other “non-routine”“non-routine” proposals only if you provide instructions to your broker on how to vote your shares by following the procedures outlined in the voting instruction form sent to you by your broker. Only Proposal No. 2 (ratifying the appointment of our independent registered public accounting firm) is considered a routine matter on which your broker may vote without instruction from you as the beneficial owner. Proposal No. 1 (election of directors) and Proposal No. 3 (advisory vote to approve named executive officer compensation) are considered non-routine matters, and without your instruction, your broker cannot vote your shares for either of Proposal No. 1 or Proposal No. 3.

Quorum and Votes Required

The inspector of elections appointed for the Annual Meeting will tabulate votes cast by proxy, telephone and via Internet at www.proxyvote.com as of 11:59 p.m. EDT on June 15, 202114, 2022 and at www.virtualshareholdermeeting.com/GH2021 on the day of andGH2022 during the Annual Meeting. The inspector of elections will also determine whether a quorum is present. In order to constitute a quorum for the conduct of business at the Annual Meeting, the holders of a majority of the shares of common stock issued and outstanding and entitled to vote at the Annual Meeting must be present or represented by proxy at the Annual Meeting. On the Record Date, there were 101,117,510101,919,898 shares of common stock entitled to vote at the Annual Meeting. Shares that abstain from voting on any proposal, or that are represented by broker non-votes, will be treated as shares that are present and entitled to vote at the Annual Meeting for purposes of determining whether a quorum is present.

Proposal No. 2: Ratification of Independent Registered Public Accounting Firm. The affirmative vote of the holders of a majority of the votes cast at the Annual Meeting is required for the ratification of the appointment of Ernst & Young as our independent registered public accounting firm. Thus, the number of votes “FOR” must exceed the number of votes “AGAINST.” Abstentions are considered to be votes not cast on this proposal and thus will have no effect. Brokers generally have discretionary authority to vote on the ratification of our independent registered public accounting firm, thus broker non-votes are not expected to result from the vote on Proposal No. 2. Any broker non-votes would be considered votes not cast and thus would have no effect.

Proposal No. 3: Advisory Vote to Approve Named Executive Officer Compensation. The affirmative vote of the holders of a majority of the votes cast at the Annual Meeting is required for determining approval on an advisory basis of the compensation of our named executive officers, as described in the “Compensation Discussion and Analysis,” executive compensation tables and accompanying narrative disclosures in our proxy materials. Abstentions and broker non-votes are considered to be votes not cast on this proposal and thus will have no effect. This vote is advisory and not binding on us, our Board, or our Compensation Committee.

In their discretion, the proxy holders named in the proxy are authorized to vote on any other matters that may properly come before the Annual Meeting and at any continuation, postponement or adjournment thereof. The Board knows of no other items of business that will be presented for consideration at the Annual Meeting other than those described in this proxy statement. In addition, no stockholder proposal or nomination was received on a timely basis, so no such matters may be brought to a vote at the Annual Meeting.

Similar to the COVID-19 pandemic, and to support the health and well-being of our Board of Directors, employees and stockholders,last year, the Annual Meeting will again be held virtually this year via live interactive audio webcast on the Internet. You will be able to attend, vote and submit your questions during the Annual Meeting by logging onto www.virtualshareholdermeeting.com/GH2021GH2022. You will not be able to attend the Annual Meeting in person.

The live audio webcast of the Annual Meeting will begin promptly at 9:30 a.m. Pacific Time. Online access to the audit webcast will open approximately 15 minutes prior to the start of the Annual Meeting to allow time for our stockholders to log in and test their devices’ audio system. We encourage our stockholders to access the meeting in advance of the designated start time.

Instructions on how to connect to the Annual Meeting, participate and demonstrate proof of stock ownership are posted on www.virtualshareholdermeeting.com/GH2021GH2022. To participate in the Annual Meeting, you will need to log-in using the 16-digit control number on your Notice, proxy card or voting instruction form.

Beginning 15 minutes prior to the start of and during the Annual Meeting, we will have a support team ready to assist stockholders with any technical difficulties they may have accessing or hearing the virtual meeting. If you encounter any difficulties accessing the virtual meeting during the check-in or meeting time, you shouldplease call ourthe technical support team at (800) 586-1548 (US Domestic Toll Free) or (303) 562-9288 (International).

Stockholders may submit questions and vote during the Annual Meeting on www.virtualshareholdermeeting.com/GH2021ww. virtualshareholdermeeting.com/GH2022. You will need to enter the 16-digit control number received with your Notice, proxy card or voting instruction form as proof of stock ownership in order to be able to submit questions and vote at our Annual Meeting. After the business portion of the Annual Meeting concludes and the meeting is adjourned, we will hold a Q&A session during which we intend to answer the questions submitted during the Annual Meeting that are pertinent to us and that are submitted in accordance with the Rules of Conduct for the Annual Meeting, as time permits. The Rules of Conduct will be posted on the virtual meeting web portal. Substantially similar questions will be answered only once. To promote fairness, efficient use our resources and to ensure all stockholder questions are able to be addressed, we will respond to no more than two questions from a single stockholder.

Our Board is soliciting proxies for the Annual Meeting from our stockholders. We will bear the entire cost of soliciting proxies from our stockholders. In addition to the solicitation of proxies by delivery of the Notice or proxy statement by mail, we will request that brokers,

A list of stockholders eligible to vote at the Annual Meeting will be available for inspection, for any purpose germane to the Annual Meeting, at our corporate headquarters for a period of no less than ten days prior to the Annual Meeting. Please contact our Corporate Secretary at CorpSecretary@guardanthealth.com if you are interested in viewing the list. The list of stockholders will also be made available on www.virtualshareholdermeeting.com/GH2021GH2022 during the Annual Meeting.

CORPORATE GOVERNANCE

Corporate Governance Focus and Stockholder Outreach

Over the course of the last year, the Board has been actively engaged in a comprehensive review of its corporate governance practices and in taking steps to strengthen and enhance those practices in response to stockholder feedback. These steps have included increasing the Private Securities Litigation Reform Actsize of 1995)the Board from seven to nine directors and increasing the gender diversity of the Board (which now consists of four women directors). These statements are based on our current expectationsMost recently, the Board also made a number of meaningful enhancements to the Company’s corporate governance structure, including:

We recognize the value of a robust stockholder outreach program. We engage in regular, constructive dialogue with our periodic reportsstockholders on Form 10-Q andmatters relevant to our current reports on Form 8-K.

The Governance Committee is mindful of the overboarding policies regarding board service of certain investors and proxy advisory firms, which policies were developed due to concerns that “overboarded” directors face excessive time commitments and challenges in fulfilling their duties. Messrs. MeresmanMr. Clark and ClarkDr. Jallal may be deemed overboarded“overboarded” under certain policies. Neither of Messrs. Meresman or Clark is up for re-election this year. Nonetheless, theThe Governance Committee reviewed and considered the contributions of Messrs. MeresmanMr. Clark and ClarkDr. Jallal to the Board and noted their strong attendance, preparedness and engagement at Board and committee meetings. The Governance Committee also noted theirMr. Clark’s valuable and extensive public company director experience and expertise (representing 2 ofand Dr. Jallal’s extensive experience in the 3 directors on our Board who currently service as board members at other public companies). Further, the Governance Committee believes that Mr. Meresman is uniquely qualified to lead our Audit Committee,biopharmaceutical industry, in particular, her expertise in drug development and note the active engagement of the other two members of our Audit Committee, who each serve on not more than one other audit committee.

The Governance Committee will consider stockholder recommendations of candidates on the same basis as it considers all other candidates. Stockholders may propose director nominees by adhering to the advance notice procedures described in the section entitled “Other Matters-StockholderMatters: Stockholder Proposals and Nominations��Nominations” in this proxy statement and must include all information as required under our Amended and Restated Certificate of Incorporation (the “Certificate of Incorporation”) and Amended and Restated Bylaws (the “Bylaws”), and any other information that would be required to solicit a proxy under federal securities laws. We may request from the recommending stockholder or recommending stockholder group such other information as may reasonably be required to determine whether each person recommended by a stockholder or stockholder group as a nominee meets the minimum director qualifications established by our Board and is independent based on applicable laws and regulations. The Governance Committee may also establish procedures, from time to time, regarding submission of candidates by stockholders and others.

Our Governance Committee and our Board have undertaken a review of the Board’s composition, the composition of Board committees and the independence of each director. Based upon information concerning each director’s background, employment and affiliations, including family relationships, the Board has affirmatively determined that each of Ian Clark, Vijaya Gadde, Bahija Jallal, Meghan Joyce, Samir Kaul, and Stanley MeresmanMyrtle Potter is independent, as defined under the applicable listing requirements and rules of the Nasdaq Global Select Market ("Nasdaq"(“Nasdaq”) and the Securities and Exchange Commission (the “SEC”), and that each of them and their respective family members have no material relationship with us, commercial or otherwise, that would interfere with the exercise of their independent judgment in carrying out the responsibilities of a director. In addition, the Board affirmatively determined that Stanley Meresman, who served as a Class I director with a term expiring at the Annual Meeting and who is not standing for re-election, was an independent director under the listing requirements and rules of the Nasdaq and SEC, and that neither he nor his family members had a relationship with us that interfered with his independent judgment in carrying out the responsibilities of a director. Drs. Eltoukhy and Talasaz were determined to not be independent due to their service as our Chief Executive Officer (“CEO”), and as our President and Chief Operating Officer (“COO”), respectively.Co-CEOs. In making these determinations, the Board

Our Board has determined that at this time it is in the best interests of the Company and our stockholders to have AmirAli Talasaz,Helmy Eltoukhy, our President and COO,Co-CEO, serve as our Chairperson of the Board, coupled with a strong lead independent director. Dr. Eltoukhy was appointed as Chairperson of the Board on August 5, 2021, succeeding AmirAli Talasaz in this role. We believe having one of our founderssenior executives serve as Chairperson promotes responsibility and accountability, and that our Board benefits from having a Chairperson with his extensive understanding of our business and the unique challenges we face. The Board believes that this structure best facilitates consistent leadership direction and long-term strategic planning, while building a cohesive corporate culture that speaks with a single voice.

Our Board also recognizes the value and importance of a strong independent lead director with clearly delineated responsibilities. The independent directors have appointed Ian Clark to serve as our lead independent director.

As set forth in our Corporate Governance Guidelines, Mr. Clark, as our independent lead director, has clearly delineated and comprehensive duties, including:

We currently have three standing committees: an Audit Committee, a Compensation Committee and a Governance Committee. From time to time, the Board may form a new committee or disband a current committee, depending on the circumstances. The charters of all three of our standing Board committees are available on our website under the “Corporate Governance-GovernanceGovernance – Governance Documents” section at https://investors.guardanthealth.com.

Audit Committee

For fiscal year 2021 and until our committee refreshment effective as of May 1, 2022, our Audit Committee consistshas consisted of Stanley Meresman, Ian Clark, and Bahija Jallal, Meghan Joyce and Myrtle Potter, with Mr. Meresman serving as chair. Ms. Joyce joined the Audit Committee upon her appointment to the Board effective August 4, 2021, and Ms. Potter jointed the Audit Committee upon her appointment to the Board effective October 15, 2021. Our Board has determined that each of these directors is independent as defined by the applicable rules of the Nasdaq and the SEC, and that each member of the Audit Committee meets the financial literacy and experience requirements of the applicable SEC and Nasdaq rules. In addition, our Board has determined that each of Messrs. Meresman and Clark, Mss. Joyce and Potter, and Dr. Jallal, is an “audit committee financial expert” as defined by the SEC. The Audit Committee met four times and acteddid not act by written consent once during the year ended December 31, 2020.

Effective as of May 1, 2022, our Audit Committee will be comprised of Stanley Meresman, as chair, Meghan Joyce and Myrtle Potter. Mr. Meresman’s service on the Board and Audit Committee will cease as of the Annual Meeting.

Our Audit Committee charter requires that the Audit Committee oversee our corporate accounting and financial reporting processes. The primary responsibilities and functions of our Audit Committee are, among other things, as follows:

Compensation Committee

For fiscal year 2021 and until our committee refreshment effective as of May 1, 2022, our Compensation Committee consistshas consisted of Ian Clark, Vijaya Gadde, Meghan Joyce, and Samir Kaul, with Mr. Clark serving as chair. Ms. GaddeJoyce joined the Compensation Committee upon her

The Compensation Committee’s responsibilities include, among other things:

reviewing and approving, or recommending that our Board approve, the compensation of our Chief Executive Officer and our other executive officers;

Since early October 2019, the Compensation Committee has engaged Radford, which is part of the RewardsAon’s Human Capital Solutions practicePractice, a division of Aon plc (“Radford”Aon”), as independent compensation consultants to provide advice and guidance on the design of our executive compensation programs and practices. RadfordAon attends Compensation Committee meetings when invited and meets with the Compensation Committee without management. RadfordAon provides the Compensation Committee with third-party data and analysis as well as advice and expertise on competitive compensation practices and trends, executive compensation plans and program designs, and proposed executive and director compensation levels. RadfordAon reports directly to the Compensation Committee and, as directed by the Compensation Committee, works with management and the chair of the Compensation Committee.

For 20202021 compensation, RadfordAon assisted the Compensation Committee onwith the following:

The Compensation Committee regularly reviews the services provided by its outside consultants, and it has assessed the independence of Radford and Semler BrossyAon consistent with SEC rules and Nasdaq listing standards. In doing so, the Compensation Committee considered each of the factors set forth by the SEC and Nasdaq with respect to a compensation consultant’s independence. The Compensation Committee also considered the nature and amount of work performed for the Compensation Committee and the fees paid for those services in relation to the firm’s total revenues. On the basis of its consideration of the foregoing and other relevant factors, the Compensation Committee has determined that each of Radford and Semler BrossyAon is independent, and that no conflicts of interest exist between the Company and each of Radford and Semler Brossy.

Nominating and Corporate Governance Committee

For fiscal year 2021 and until our committee refreshment effective as of May 1, 2022, our Governance Committee consists of Samir Kaul, Stanley Meresman and Bahija Jallal, with Mr. Kaul serving as chair. Our Board has determined that each of Messrs. Kaul and Meresman, and Dr. Jallal, is independent under Nasdaq rules. The Governance Committee met threefour times and acted by written consent once during the year ended December 31, 2020.

In response in part to stockholder feedback, the Board recently reviewed and enhanced the oversight responsibilities of the Governance Committee. The Governance Committee’s responsibilities include, among other things:

identifying individuals qualified to become Board members;

The Audit Committee of the Board is primarily responsible for overseeing our risk management processes on behalf of the Board. The Audit Committee receives reports from

Each of our committees periodically provide updates to the Board regarding significant risk management issues and management’s response.

We have adopted a written Business Code of Conduct and Ethics that applies to our directors, officers and employees, including our principal executive officer, principal financial officer, principal accounting officer or controller, or persons performing similar functions. In February 2022, our Board amended the Code of Conduct to increase the breadth and specificity of standards to be upheld by all directors, officers and employees of the Company, including adding and refining guidelines regarding conflicts of interest, business records, gifts and favors, antitrust practices, political contributions, environmental protection, and personal conduct and social media practices. We have posted a current copy of the code on our website, https://investors.guardanthealth.com.investors.guardanthealth.com. In addition, we intend to post on our website all disclosures that are required by law or the listing standards of Nasdaq concerning any amendments to, or waivers from, any provision of the code.

Environmental, Social and Governance

Guardant’s Values. This year marks the last quartertenth anniversary of 2020Guardant Health. As we were approaching our anniversary, we knew we needed to evolve our values to reflect the future growth of the organization and into the first quarterto be intentional with our culture. Our core values guide what we do each and every day in pursuit of 2021, we conducted outreach to engage with stockholdersour mission. We embarked on a wide variety of topicssix-month journey that involved working with senior leaders and identifying culture champions across the organization who understand the company culture and how work gets done. We held several working sessions and gained valuable insights and opinions from our senior leaders and culture champions until we landed on values that are importantactionable, easy to them. We report backarticulate and relevant to our Board on this engagement as well as specific issues to be addressed.

Environmental, Social and Governance (ESG) Commitment. Our vision is reinforced through rigorous policies, educationto transform the biotechnology industry by creating impactful diagnostic tools that will be affordable and engagement of our employees and internal and external periodic audits.

We expect to release our first ESG annual report in the first half of 2023.

Grants and Giving. We sponsor and support numerous non-profits and patient advocacy groups and our employees strategically align talent within our organizationdonate their time. Our contributions help to support the work of non-profit organizations of all sizes, working in areas such as cancer research and reward performance, while also managingpatient support, community wellness and scientific education, and supporting the costsmission to accelerate access to innovation for cancer patients.

Safety and Wellness. We are committed to providing a safe and secure work environment and maintaining environmental, health and safety policies that seek to promote the health and safety of such policies and programs. We provide our employees with competitiveand patients. We mandate continual training programs, and we have a robust employee wellness program that recognizes and supports the importance of personal health and work-life balance. We are committed to rewarding, supporting, and developing the employees who make it possible to deliver on our strategy. To that end, we offer a comprehensive total rewards package that includes market-competitive fixed and/or variable pay, competitive Companybroad-based equity programs,grants and bonuses, access to medical, dental, vision and life insurance benefits, disability coverage, a 401(k)fertility subsidies, retirement savings planplans, paid time off and numerous wellbeing benefits throughfamily leave, caregiving support, fitness, cellphone and internet reimbursements, and mental health and other wellness benefits.

Governance. We evaluate input from our Total Rewards program.

In February 2022, our Board amended our Governance Committee Charter to enhance the Company.

Any interested person, including any stockholder, may communicate with our Board by written mail addressed to Guardant Health, Inc. Board of Directors, c/o Corporate Secretary,

Process for Determining Director Compensation Program. Prior toDecisions regarding the non-employee director compensation program are approved by our annual stockholders meeting in 2020, our Directorfull Board based on recommendations by the Compensation Program consisted of the following components:

The Board believes that replacing a more traditional cash-and-equity compensation program with anadopted its current equity-only compensation program, is more competitive when compared to our peers; in addition, the total cost of the program, on an annual basis, approximates the total compensation cost of our peer groups’ director compensation programs. In addition, the initial equity awards granted to incoming directors under the updated program vest over four years, which is longer than our peer group (which use three years). In determining to incorporate an additional equity award to our Lead Independent Director, our Board took into account the significant role and scope of this director’s responsibilities, including leading meetings of independent directors and providing input on meeting agendas, advising our CEO as to quantity, quality and timeliness of information and materials, providing feedback to our CEO on the CEO’s evaluation and leading the Board evaluation process.

The Initial Award is granted to each non-employee director who is initially elected or appointed to serve on the Board and each Initial Award vests and becomes exercisable (as applicable) as to 25% of the shares subject to such award on the first anniversary of the director’s election to the Board, and as to the remaining 75% of the shares subject to the Initial Award in substantially equal installments on each monthly anniversary of the director’s election to the Board thereafter, subject to continued service through the applicable vesting date.

The Annual Award is granted on the date of each annual stockholders’ meeting to non-employee directors who have served on the Board for at least six months prior to the date of such annual stockholders’ meeting. Each Annual Award vests and become exercisable (as applicable) in full on the earlier to occur of (i) the one-year anniversary of the applicable grant date and (ii) the date of the next annual meeting of the Company’s stockholders following the grant date, subject to continued service through the applicable vesting date.

The LID Award is granted on the date of each annual stockholders’ meeting to the non-employee director who has served on the Board for at least six months as of the date of such annual stockholders’ meeting and who will also serve as Lead Independent Director of the Board immediately following such meeting. Each LID Award will vest in full on the earlier to occur of (i) the one-year anniversary of the applicable grant date and (ii) the date of the next annual meeting of the Company’s stockholders following the grant date, subject to continued service through the applicable vesting date.

In addition, each Initial Award, Annual Award and LID Award will vest in full immediately prior to the director’s death, disability, termination without cause, or a change in control (as defined in the 2018 Plan)Incentive Award Plan (the “2018 Plan”)).

Any compensation payable to a director under this updated program will comply with the director annual compensation limit set forth in our 2018 Plan (currently, an annual limit of $750,000 per director).

Director Compensation Table. The following table contains information concerning the compensation received by our non-employee directors during the year ended December 31, 2020.2021. Directors who are also employees do not receive compensation for service on our Board (in addition to the compensation payable for their service as our employees). Drs. Eltoukhy and Talasaz are not included in the table below because they did not receive any additional compensation for their service on our Board. Drs. Eltoukhy’s and Talasaz’s 2021 compensation is presented in the Summary Compensation Table found on page 60.

Pursuant to our Certificate of Incorporation and our Bylaws, the total number of directors constituting the Board is fixed from time to time by the Board. There are currently sevennine authorized directors and sevennine persons serving as directors. The Board has reduced the authorized number of directors effective as of the Annual Meeting to eight members.

The Board is divided into three classes (Class I, Class II and Class III) with staggered terms of three years each and holding office until his or her successor is duly elected and qualified, or until his or her earlier resignation or removal Each class contains as nearly as possible an equal number of directors. The term of one class expires at each annual meeting of stockholders; thus, directors typically stand for election after three years, unless they are filling an unexpired term. The current term of office of our Class I Directors expires at the Annual Meeting, while the term for our Class II Directors will expire at our 2023 annual meeting of stockholders and the term for our Class III Directors expires at our 2024 annual meeting of stockholders. On June 12, 2020, Vijaya GaddeAugust 4, 2021, Meghan Joyce was appointed to the Board as a Class II director to serve for a term expiring at our 2023 annual meeting of stockholders. On October 15, 2021, Myrtle Potter was appointed to the Board as a Class I director to serve for a term expiring at our 2022 annual meeting of stockholders. With the addition of Ms. Gadde, two of our seven directors are women.

Based upon the recommendation of our Governance Committee, the Board has nominated each of Helmy Eltoukhy, AmirAli TalasazVijaya Gadde and Bahija Jallal,Myrtle Potter, each a current Class IIII Director, for re-election at the Annual Meeting. Each director elected at the Annual Meeting will serve a three-year term expiring at the 20242025 annual meeting of stockholders and until his or her successor is duly elected and qualified as a Class IIII Director, or until his or her earlier death, resignation or removal. At the Annual Meeting, proxies cannot be voted for a greater number of individuals than the threetwo nominees named in this proxy statement.

The Board and the Governance Committee believe the skills, qualities, attributes and experience of our directors provide us with business acumen and a diverse range of perspectives to engage each other and management to effectively address effectively our evolving needs and represent the best interests of our stockholders.

Vacancies on the Board, including any vacancy created by an increase in the size of the Board, may be filled only by a majority of the directors remaining in office, even though less than a quorum of the Board, or a sole remaining director. A director elected by the Board to fill a vacancy will serve until the next election of the class of directors for which such director was chosen and until such director’s successor is elected and qualified, or until such director’s earlier retirement, resignation, disqualification, removal or death.

If any nominee should become unavailable for election prior to the Annual Meeting, an event that currently is not anticipated by the Board, the proxies will be voted in favor of the election of a substitute nominee or nominees proposed by the Board or the number of directors may be reduced accordingly. Each nominee has agreed to serve if elected and the Board has no reason to believe that any nominee will be unable to serve.

Set forth below is biographical information for each nominee and a summary of the specific qualifications, attributes, skills and experiences which led the Board to conclude that each nominee should serve on the Board at this time.

EXECUTIVE OFFICERS

The following sets for the biographical information of our Executive Officers. Biographical information pertaining to Helmy Eltoukhy, who is a memberour Chairperson of ourthe Board and our CEO,Co-CEO, and AmirAli Talasaz, who is the Chairpersona member of ourthe Board and our President and COO,Co-CEO, may be found in the section above entitled “Proposal 1: Election of Directors – Information about Other Directors Not Standing for Election at this Meeting – Class III Director Nominees.”

Michael Bell. Bell.Mr. Bell has served as our Chief Financial Officer since January 2021. He most recently served as the Chief Financial Officer of CareDx, Inc., a precision medicine company focused on transplantation, from April 2017 to December 2020. From January 2016 to March 2017, Mr. Bell served as the Chief Financial Officer of Metabiota, Inc., a company that develops and sells risk analytics products focused on infectious disease. From May 2012 to January 2016, he served as the Chief Financial Officer of Singulex, Inc., a clinical diagnostics company. Prior to that, Mr. Bell held leadership and executive positions within Novartis, including with Novartis Diagnostics, a global provider of blood screening solutions, where he served as Chief Financial Officer from 2011 to 2012, and Senior Director, Global Head of Finance from 2008 to 2011. Mr. Bell also previously worked for several years in public accounting with both Ernst & Young and Deloitte, UK. He holds a Bachelor of Science degree in Mathematics with Computing from the University of Leicester in the United Kingdom and is a Fellow of the Institute of Chartered Accountants in England & Wales.

Craig Eagle, M.D. Dr. Eagle has served as our Chief Medical Officer since April 2021. He most recently served as Vice President of Medical Affairs Oncology for Genentech, a company that uses human generic information to develop, manufacture and sell medicines for serious conditions, from 2019 to 2021, where he oversaw the medical programs across the oncology portfolio and developed innovative cancer trials and strategies in personalized health care. Prior to Genentech, Dr. Eagle has held several positions in the U.S. and internationally at Pfizer, from 2009 to 2019, including global head of the Oncology Medical

EXECUTIVE COMPENSATION

COMPENSATION DISCUSSION AND ANALYSIS

This Compensation Discussion and Analysis (“CD&A”) discusses the principles and objectives underlying our policies and decisions with respect to the compensation of our named executive officers (“NEOs”) and other material factors relevant to an analysis of these policies and decisions regarding our 20202021 executive compensation program. This CD&A is intended to be read in conjunction with the tables that immediately follow this section, which provide further compensation information for the followingour 2021 NEOs:

We are a leading precision oncology company focused on helping conquer cancer globally through the use of our proprietary blood-based tests, vast data sets and advanced analytics. Today our proprietary tests are helping to realize the full potential of precision oncology by providing patients and their doctors critical insights that can inform decisions at all stages of the disease, from screening, to monitoring cancer recurrence, to treatment decisions. We believe that the key to conquering cancer is unprecedented access to its molecular information throughout all stages of the disease, which we intend to enable by our tests. By looking at the

In February 2021, we launched our Guardant Reveal liquid biopsy-based testtests for residual and recurring cancer to first address the need in Stage II-III colorectal cancer.

In June 2021, we launched Guardant360 TissueNext, our Guardant360 tissue programfirst tissue-based test which aimswill be used to address challenges with tissue genotyping products currently available in the market and are also developing tests from our LUNAR program which aims to address the needs of early-stage canceridentify patients with neoadjuvantadvanced cancer who may benefit from biomarker-informed treatment, and adjuvantGuardant360 Response which will be used to measure early indications to patients’ response to treatment selection, cancer survivors with surveillance, and asymptomatic individuals eligible for cancer screening and individuals at a higher risk for developing cancer with early detection.up to eight weeks earlier than response evaluation criteria in solid tumors. We have also developed our GuardantINFORM platform to further accelerate precision oncology drug development by biopharmaceutical companies by offering them an in-silico research platform to unlock further insights into tumor evolution and treatment resistance across various biomarker-driven cancers.

Most recently, we implemented a set of values and core beliefs for the FDA as a breakthrough device for use as a companion diagnostic in connection with certain specified therapeutic products ofCompany to drive cultural change and create an environment centered on patient care, collaboration, inclusion and innovation. For more information on our biopharmaceutical customers.

We believe our tests can expand the scope of precision oncology to earlier stages of the disease, improve patient outcomes and lower healthcare costs.

Stockholder Engagement

General. We recognize the value of a robust stockholder outreach program. We engage in regular, constructive dialogue with our stockholders on matters relevant to our business, including corporate governance, executive compensation, strategy, ESG issues and human capital management. We believe that our approach to engaging openly with our stockholders drives increased corporate accountability, improves decision making, and ultimately creates long-term value.

Robust Stockholder Engagement

At our 2021 Annual Meeting, we are no longer considered an “emerging growth company” as defined underreceived approximately 38% support of the Jumpstart Our Business Startups Actvotes cast on our Say-on-Pay proposal. In addition to the outreach conducted in the weeks leading up to our 2021 annual meeting of 2012, we will be holdingstockholders (the “2021 Annual Meeting”), following our first non-binding stockholderreview of the results of the shareholder advisory vote on the compensation of our named executive officers (a “Say-on-Pay” vote) at the 2021 Annual Meeting. ThroughoutMeeting, we again reached out to stockholders to solicit feedback. During the last quarterthird and fourth quarters of 20202021 and into the first quarter of 2021,2022, we reached out tocontacted our top 2075 stockholders, representing over 54%more than 86% of the totalCompany’s outstanding shares of common stock. We ultimately spoke with 25 stockholders representing approximately 57% of the Company’s outstanding shares of common stock, including at least 10 institutions that voted “against” our Say-on-Pay proposal last year. Eight of these stockholders, representing approximately 6% of the Company’s outstanding shares of common stock, declined and indicated a meeting with the Company was not necessary, while 17 of these stockholders, representing approximately 51% of the Company’s outstanding shares of common stock, engaged with us and provided substantive feedback. We also engaged with the research teams at proxy advisory firms Institutional Shareholder Services Inc. and Glass Lewis & Co. to discuss various matters, includinghear their feedback regarding our executive compensation program. We are committed to engagingprograms.

The Compensation Committee Chair (when requested), together with stockholders to ensure that we understand stockholder feedback aboutthe Senior Vice President, General Counsel and Secretary, our executive compensation programsVice President of Investor Relations, and other key mattersmembers of interest to them,the corporate legal team, participated in this effort on behalf of the Company. All feedback received was shared and we pay careful attention to any feedback we receive from them. We intend to continue our stockholder outreach following the filing of this proxy statementdiscussed with the SEC, to seek support for our annual meeting proposals and to solicit additional feedback regarding compensation and governance matters of importance to our stockholders.