Plasma fibrinogen is strongly associated with cardiovascular morbi-mortality. We investigated in the large cohort of the D.E.S.I.R. (data from an epidemiological study on the insulin resistance syndrome) study, the relationship between change in fibrinogen concentration over a 3-year follow-up and fibrate and statin use. Fibrinogen concentrations were higher at baseline among individuals treated with statins (n=130) compared to those treated with fibrates (n=251), even after adjustment for confounding factors (including total cholesterol, HDL cholesterol and triglycerides) (mean (S.D.): 2.8 (0.6) vs. 3.1 (0.6), P<0.001). We compared change in fibrinogen concentrations at 3 years of follow-up, between individuals who started fibrate (n=126) or statin (n=127) treatment during the follow-up and individuals (n=3906) who stayed without treatment during this period. After adjustment for baseline fibrinogen level, age, sex and changes in total cholesterol, triglycerides and alcohol intake, fibrinogen concentration decreased after fibrate treatment, while it increased after statin treatment and in those not using lipid lowering drugs (-0.07 (0.54) vs. 0.10 (0.54) vs. 0.08 (0.52) g/l respectively, P=0.01). No differences were observed between different statins or different fibrates. In conclusion, fibrates in contrast with statins may combine lipid-lowering with a beneficial effect on fibrinogen. This effect is independent of changes in cholesterol and triglyceride concentrations.