Background: Several clinical trials have reported inconsistent findings for the effect of fibrates on cardiovascular risk. We undertook a systematic review and meta-analysis to investigate the effects of fibrates on major clinical outcomes. Methods: We systematically searched Medline, Embase, and the Cochrane Library for trials published between 1950 and March, 2010. We included prospective randomised controlled trials assessing the effects of fibrates on cardiovascular outcomes compared with placebo. Summary estimates of relative risk (RR) reductions were calculated with a random effects model. Outcomes analysed were major cardiovascular events, coronary events, stroke, heart failure, coronary revascularisation, all-cause mortality, cardiovascular death, non-vascular death, sudden death, new onset albuminuria, and drug-related adverse events. Findings: We identified 18 trials providing data for 45 058 participants, including 2870 major cardiovascular events, 4552 coronary events, and 3880 deaths. Fibrate therapy produced a 10% RR reduction (95% CI 0-18) for major cardiovascular events (p=0·048) and a 13% RR reduction (7-19) for coronary events (p<0·0001), but had no benefit on stroke (-3%, -16 to 9; p=0·69). We noted no effect of fibrate therapy on the risk of all-cause mortality (0%, -8 to 7; p=0·92), cardiovascular mortality (3%, -7 to 12; p=0·59), sudden death (11%, -6 to 26; p=0·19), or non-vascular mortality (-10%, -21 to 0·5; p=0·063). Fibrates reduced the risk of albuminuria progression by 14% (2-25; p=0·028). Serious drug-related adverse events were not significantly increased by fibrates (17 413 participants, 225 events; RR 1·21, 0·91-1·61; p=0·19), although increases in serum creatinine concentrations were common (1·99, 1·46-2·70; p<0·0001). Interpretation: Fibrates can reduce the risk of major cardiovascular events predominantly by prevention of coronary events, and might have a role in individuals at high risk of cardiovascular events and in those with combined dyslipidaemia. Funding: National Health and Medical Research Council of Australia. © 2010 Elsevier Ltd. All rights reserved.