BACKGROUND AND AIM: Impaired triglyceride-rich lipoprotein metabolism is most probably related to an enhanced cardiovascular risk, and may be associated with a pro-coagulant state. A double-blind, randomized study was undertaken to evaluate two widely utilized hypolipidemic drugs in the post-prandial phase and their impact on lipid, coagulation and fibrinolytic parameters. METHODS AND RESULTS: Thirty middle-aged men selected according to their low density lipoprotein-cholesterol (LDL-C) > or = 160 and < or = 240 mg/dl and borderline hypertriglyceridemia (110-220 mg/dl) after at least one month of a lipid-lowering diet received gemfibrozil (600 mg bid) or simvastatin (20 mg qd) and the corresponding placebo. On enrollment and after 2 months of drug treatment, they were tested with a standard oral fat load (OFL) (35 g fat/m2 body surface). On both occasions plasma total-cholesterol, LDL-C, HDL-C, triglycerides, lipoprotein[a] (Lp[a]), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), antithrombin-III (AT-III), plasminogen and fibrinogen were determined just before the meal (t0) and at times 2 hours, 4 h, 6 h, 8 h after it (t2-t8). A two-factor (time and visit) multivariate analysis for repeated measurements was performed to evaluate the data. Total cholesterol, and LDL-C were significantly diminished 2 months after both gemfibrozil and simvastatin, the latter being more active. Plasma triglycerides showed a marked reduction with gemfibrozil at all times, while simvastatin regimen yielded only minor modifications. HDL-C was only slightly increased by simvastatin; Lp[a] plasma levels were almost unaffected. Small fibrinogen (t0, t2, t6, t8), PAI-1 (t6) and AT III (t0-t8) increases were observed after gemfibrozil, while simvastatin did not significantly modify these parameters. CONCLUSIONS: In the post-prandial phase, gemfibrozil and simvastatin induce different metabolic effects that beneficially influence the lipid pattern, whereas fibrinolytic and coagulative parameters display minor variations of undetermined significance.