IMPORTANCE Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart disease, but large trials of omega-3 fatty acids have produced conflicting results. OBJECTIVE To conduct ameta-analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups. DATA SOURCES AND STUDY SELECTION This meta-analysis included randomized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events. DATA EXTRACTION AND SYNTHESIS Aggregated study-level datawere obtained from 10 large randomized clinical trials. Rate ratios for each trial were synthesized using observed minus expected statistics and variances. Summary rate ratios were estimated by a fixed-effects meta-analysis using 95%confidence intervals for major diseases and 99%confidence intervals for all subgroups. MAIN OUTCOMES AND MEASURES The main outcomes included fatal coronary heart disease, nonfatalmyocardial infarction, stroke, major vascular events, and all-cause mortality, as well as major vascular events in study population subgroups. RESULTS Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatalmyocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99%CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99%CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95%CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use. CONCLUSIONS AND RELEVANCE This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease.