It is now agreed that the majority of acute myocardial infarctions result from intracoronary thrombosis at sites of atherosclerotic plaque that have been disrupted. In 1947 Nicol and Fassett published the first clinical paper suggesting that agents interfering with blood coagulation could prevent myocardial infarction in patients at risk. Scores of subsequent clinical trials were performed to assess the efficacy of anticoagulants and antiplatelet agents in preventing death and reinfarction in survivors of acute myocardial infarction. Despite these efforts no agreement exists on whether these strategies are beneficial and, if so, which is superior. The primary obstacle to progress in this field has been the failure of nearly all trials to enroll the large numbers of subjects required to demonstrate a survival benefit. The large sample size requirement derives from two inescapable facts: mortality rates following acute infarction, though variable, are generally low and the potential benefit of these agents in preventing mortality is small. Combining oral anticoagulants with antiplatelet agents (combination hemotherapy) may significantly enhance their antithrombotic effect. Clinical trials of combination hemotherapy have demonstrated superiority over anticoagulant monotherapy in the setting of stroke prevention in patients with prosthetic heart valves. Similar benefit was not observed in trials studying stroke prevention in nonvalvular atrial fibrillation and vascular morbidity in patients surviving an acute myocardial infarction. The failure of these latter studies may relate to the particularly low intensity of warfarin administered in combination with aspirin. This trial proposes to demonstrate that the combination of oral anticoagulation, administered in a moderate dose intensity, and antiplatelet therapy is superior to aspirin monotherapy in reducing overall mortality following acute myocardial infarction.