BACKGROUND: Several studies suggest differences between fibrates and statins in lowering plasma fibrinogen (Fib) concentrations, but the evidence is not definitive. Therefore, the aim of this meta-analysis of head-to-head randomized trials was to compare the efficacy of statins and fibrates on plasma Fib concentrations. METHODS: The literature search included Medline, Scopus, and Web of Science up to February 1st, 2015, to identify head-to-head comparative randomized trials investigating the efficacy of fibrates vs statins on plasma Fib concentrations. RESULTS: In total 22 trials with 2762 participants were included to the meta-analysis. Random-effect meta-analysis suggested a significantly greater effect of fibrates vs statins in lowering plasma Fib concentrations (weighted mean difference [WMD]: -40.7mg/dL, 95% confidence interval [CI]: -55.2, -26.3, p<0.001). When the analysis was stratified according to the type of fibrate administered, there were significant Fib-lowering effects with both bezafibrate (n=8 treatment arms; WMD: -23.7mg/dL, 95% CI: -41.8, -5.7, p=0.01) and fenofibrate (n=15 treatment arms; WMD: -43.7mg/dL, 95% CI: -61.3, -26.2, p<0.001). Overall, there was a numerically greater effect in the subgroup of trials with ≥12 weeks duration (n=17 treatment arms; WMD: -42.7mg/dL, 95% CI: -60.3, -25.1, p<0.001) compared with the subgroup of trials lasting <12 weeks (n=7 treatment arms; WMD: -36.7mg/dL, 95% CI: -52.0, -21.4, p<0.001). CONCLUSIONS: Monotherapy with either fibrates or statins suggested a significantly greater effect of fibrates in lowering plasma Fib concentrations. According to these findings, mechanisms associated with fibrinogen metabolism might be responsible for the distinct effects of statins and fibrates in reducing cardiovascular endpoints.