Background: Lipoprotein(a) is a risk factor for cardiovascular events and modifies the benefit of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. Lipoprotein(a) concentration can be measured with immunoassays reporting mass or molar concentration or a reference measurement system using mass spectrometry. Whether the relationships between lipoprotein(a) concentrations and cardiovascular events in a high-risk cohort differ across lipoprotein(a) methods is unknown. We compared the prognostic and predictive value of these types of lipoprotein(a) tests for major adverse cardiovascular events (MACE)., Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the PCSK9 inhibitor alirocumab with placebo in patients with recent acute coronary syndrome. We compared risk of a MACE in the placebo group and MACE risk reduction with alirocumab according to baseline lipoprotein(a) concentration measured by Siemens N-latex nephelometric immunoassay (IA-mass; mg/dL), Roche Tina-Quant turbidimetric immunoassay (IA-molar; nmol/L), and a noncommercial mass spectrometry-based test (MS; nmol/L). Lipoprotein(a) values were transformed into percentiles for comparative modeling. Natural cubic splines estimated continuous relationships between baseline lipoprotein(a) and outcomes in each treatment group. Event rates were also determined across baseline lipoprotein(a) quartiles defined by each assay., Results: Among 11 970 trial participants with results from all 3 tests, baseline median (Q1, Q3) lipoprotein(a) concentrations were 21.8 (6.9, 60.0) mg/dL, 45.0 (13.2, 153.8) nmol/L, and 42.2 (14.3, 143.1) nmol/L for IA-mass, IA-molar, and MS, respectively. The strongest correlation was between IA-molar and MS (r=0.990), with nominally weaker correlations between IA-mass and MS (r=0.967) and IA-mass and IA-molar (r=0.972). Relationships of lipoprotein(a) with MACE risk in the placebo group were nearly identical with each test, with estimated cumulative incidences differing by ≤0.4% across lipoprotein(a) percentiles, and all were incrementally prognostic after accounting for low-density lipoprotein cholesterol levels (all spline P ≤0.0003). Predicted alirocumab treatment effects were also nearly identical for each of the 3 tests, with estimated treatment hazard ratios differing by ≤0.07 between tests across percentiles and nominally less relative risk reduction by alirocumab at lower percentiles for all 3 tests. Absolute risk reduction with alirocumab increased with increasing lipoprotein(a) measured by each test, with significant linear trends across quartiles., Conclusions: In patients with recent acute coronary syndrome, 3 lipoprotein(a) tests were similarly prognostic for MACE in the placebo group and predictive of MACE reductions with alirocumab at the cohort level., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402., Competing Interests: Disclosures Dr Szarek reports serving as a consultant or receiving research support, or both, from CiVi, Resverlogix, Lexicon, Baxter, Esperion, Amarin, NewAmsterdam, Sanofi, and Regeneron Pharmaceuticals, Inc. E. Reijnders reports no disclosures. Dr Jukema reports research grants from the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands, and the European Commission Seventh Framework Programme, and research support from Amgen, Astellas, AstraZeneca, Daiichi-Sankyo, Lilly, Merck-Schering-Plough, Novartis, Pfizer, Roche, and Sanofi. Dr Bhatt was on advisory boards of Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; was on boards of directors of Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; was inaugural chair of the American Heart Association quality oversight committee; was a consultant for Broadview Ventures and Hims; was on data monitoring committees of Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; and for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT Trial); received honoraria from American College of Cardiology (senior associate editor, “Clinical Trials and News,” ACC.org; chair, ACC accreditation oversight committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee, funded by Boehringer Ingelheim; AEGIS-II executive committee, funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor and associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees), and Wiley (steering committee); additional disclosures: Clinical Cardiology (deputy editor), NCDR-ACTION registry steering committee (chair), and VA CART research and publications committee (chair); patent: sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, assigned to Lexicon; Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site coinvestigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; unfunded research: FlowCo and Takeda. Dr Bittner reports grant support from Sanofi, Regeneron Pharmaceuticals, Amgen, Astra Zeneca, DalCor, Esperion, and Novartis; consulting fees from Pfizer; honoraria from Medscape; and fees for participating on data safety monitoring boards for the National Institutes of Health and for Verve Therapeutics. Dr Diaz reports research grants from Sanofi, DalCor Pharmaceuticals, Population Health Research Institute, Duke Clinical Research Institute, the TIMI group, Amgen, Cirius, Montreal Health Innovations Coordinating Center, and Lepetit; and personal fees, as a member of the Executive Steering Committee, from Amgen and Cirius. Dr Fazio is an employee of Regeneron Pharmaceuticals Inc and may hold shares in the company. G. Garon is an employee of Sanofi and may hold shares in the company. Dr Goodman reports research grant support (eg, steering committee or data and safety monitoring committee) or speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, and Valeo Pharma; and salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) chair, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and the TIMI Study Group (Brigham Health). Dr Harrington reports research grants from the Patient-Centered Outcomes Research Institute, National Institutes of Health, CSL, and Janssen; consulting for Atropos Health, Bitterroot Bio, Bridge Bio, Bristol Myers Squibb, Foresight, and Element Science; and served on the boards of directors for the American Heart Association (unpaid) and Cytokinetics. Dr Ruhaak reports no disclosures. Dr Schwertfeger is an employee of Roche and may hold shares in the company. Dr Tsimikas is a coinventor and receives royalties from patents owned by University of California San Diego and is a cofounder and has an equity interest in Oxitope, LLC, and its affiliates, Kleanthi Diagnostics, LLC, and has a dual appointment at the University of California San Diego and Ionis Pharmaceuticals. Dr White reports grant support paid to the institution for serving on a steering committee for the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) from Sanofi-Aventis and Regeneron Pharmaceuticals, for ACCELERATE (A Study of Evacetrapib in High-Risk Vascular Disease) from Eli Lilly and Company, for STRENGTH (Outcomes Study to Assess Statin Residual Risk Reduction With EpaNova in High CV Risk Patients With Hypertriglyceridemia) from Omthera Pharmaceuticals, for CAMELLIA-TIMI (A Study to Evaluate the Effect of Long-term Treatment With BELVIQ [Lorcaserin HC] on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk Factors) from Eisai Inc, for HEART-FID (Randomized Placebo-Controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency) from American Regent, and for ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) and the MINT Trial (Myocardial Ischemia and Transfusion) from the National Institutes of Health; received grants to the institution and personal fees as a steering committee member for the Dal-Gene study (Effect of Dalcetrapib versus Placebo on CV Risk in a Genetically Defined Population With a Recent ACS) from DalCor Pharma UK Inc, for the AEGIS-II study (The Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Human ApoA-I, After Acute Myocardial Infarction: The ApoA-I Event Reducing in Ischemic Syndromes I) from CSL Behring, for the SCORED trial (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and the SOLOIST-WHF trial (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure) from Sanofi-Aventis Australia Pty Ltd, and for the CLEAR Outcomes Study (Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid [ETC-1002] or Placebo) from Esperion Therapeutics Inc; and was on advisory boards for CSL Behring and Genentech, Inc (an affiliate of F. Hoffmann–La Roche Ltd, “Roche”; Lytics Post-PCI advisory board at European Society of Cardiology). Dr Steg reports grants, personal fees, and nonfinancial support from Sanofi; grants and personal fees from Amarin, Servier, and Bayer; and personal fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Idorsia, Pfizer, and Novartis. Dr Cobbaert reports research collaboration with Roche Diagnostics. Dr Schwartz reports research grants to the University of Colorado from AstraZeneca, Resverlogix, Sanofi, Silence Therapeutics, and The Medicines Company; and is coinventor of pending US patent 62/806,313 (“Methods for Reducing Cardiovascular Risk”) assigned in full to the University of Colorado.