The effects of fatty acids on hemostasis are controversial. It has been difficult to show convincing effects of saturated or monounsaturated fatty acids that are clearly related to hemostatic variables in humans. Unsaturated fatty acids alter platelet aggregation and processes related to coagulation and fibrinolysis. Indirect evidence exists that n-6 polyunsaturated fatty acids may exert favorable effects on thrombotic processes in vivo, but large clinical trials have failed to show benefits of 5-6 g linoleic acid (18:2n-6) or linolenic acid (18:3n-3)/d. Only long-chain n-3 fatty acids prolong the template bleeding time, and they may exert some beneficial effect on erythrocyte flexibility. It appears unlikely that n-3 fatty acids lower fibrinogen or interact with the fibrinolytic system directly. One prospective secondary prevention trial showed benefits that may have resulted from either an improved hemostatic profile or an antiarrhythmic effect. A similar time course of clinical improvement was noted with reduced rates of cardiac mortality and postoperative thrombosis in Norway during World War II, and this was associated with a drastic dietary alteration involving increased consumption of n-3 fatty acids and reduced consumption of saturated fatty acids. Further work is needed to develop better tools to examine in vivo hemostasis so that the mechanisms and eventual clinical utility of n-3 fatty acids can be elucidated in well-designed clinical trials.