According to recently published data, fibrates may reduce the risk of major cardiovascular events. Whether patients with low high-density lipoprotein cholesterol (HDL-C), high triglyceride levels, or both may have additional benefits remains under debate.We performed a meta-analysis of the 5 large trials assessing the impact of fibrates on cardiovascular end points and providing information on low HDL-C and high triglyceride levels. Subgroups were determined according to values closest to predetermined cut-offs for both HDL-C and triglycerides (<35 and >200 mg/dL, respectively). Overall, 4671 patients (2401 in fibrate group and 2270 in placebo group) were classified as having an atherogenic dyslipidemia featuring low HDLC combined with high triglyceride levels. Across trials, the proportion of patients classified in this subgroup ranged from 11% to 33%. We found a significant difference in the magnitude of fibrate effect across dyslipidemia subgroups (P for between-group heterogeneity = 0.0002). A greater effect size was found in patients with high triglyceride levels or atherogenic dyslipidemia phenotype where fibrates were estimated to reduce the cardiovascular risk by 28% [95% confidence interval (CI), 15% to 39%; P < 0.001] or 30% (95% CI, 19% to 40%, P < 0.0001), respectively, but only by 6% (95% CI, 22% to 13%, P = 0.13) in nonatherogenic dyslipidemia patients. Targeting patients with high triglyceride levels or atherogenic dyslipidemia with fibrates may help reduce residual vascular risk.