The aims of this double-blind study were to examine whether in hypertriglyceridemic men the ingestion of a standardized fatty meal alters hemostasis negatively and whether triglyceride-lowering treatment with etofibrate for 6 weeks alters fasting and postprandial hemostasis positively, thus reversing the potential negative effects of a fatty meal on postprandial hemostasis. To answer these questions, we measured markers of hemostasis immediately before a standardized fatty meal, and 4, 6, 8, and 10 hours after the meal in 21 hypertriglyceridemic men both before and after treatment with etofibrate. We found that the concentration of plasmin alpha2antiplasmin complex markedly increased for at least 10 hours after the fatty meal, but that the activation of factor XII and the concentration of prothrombin activation fragment1+2 decreased after the fatty meal. These results on factor XII contradict reported in vitro data. Triglyceride-lowering treatment with etofibrate in 10 of these men for 6 weeks increased fasting and postprandial protein C and plasminogen and also slightly decreased the activation of fXII; however, it did not reverse the postprandial increase of PAP or change the decrease of prothrombin activation fragment1+2. Our findings indicate that postprandial lipoproteins alter markers of hemostasis positively in an antithrombotic and profibrinolytic direction. In addition, triglyceride-lowering treatment with etofibrate only slightly improves markers of fasting and postprandial hemostasis in an antithrombotic and profibrinolytic direction.