Platelet reactivity to shear stress and collagen and dynamic overall coagulation were measured in vitro from nonanticoagulated blood of 137 patients on warfarin. One hundred five matched, healthy subjects served as controls. Platelet reactivity to both stimuli and contribution of platelets to plasmatic coagulation were significantly inhibited in patients on warfarin. No correlation was found between platelet reactivity and the coagulation status assessed by the international normalized prothrombin time ratio (INR). Despite similar INR, platelet reactivity showed great individual variation. In 98 patients who were followed up for 3 months, measurement of platelet reactivity to shear stress could discriminate between those who had either bleeding or thromboembolic episodes. These findings suggest that monitored platelet function would help in individualizing oral anticoagulant regimens and hence would increase the benefit of therapy without the risk of bleeding complications.