Objectives, This study assessed whether combination therapy with aspirin and warfarin for 10 weeks reduces the risk of progression or reocclusion of the unstable coronary artery lesion, Background, Reocclusion of the culprit coronary artery occurs in up to one third of patients during the 3 months after myocardial infarction (MI) or unstable angina and is associated with increased morbidity and mortality, Methods, Fifty-seven patients presenting with unstable angina or MI who had an identifiable culprit lesion at coronary angiography were randomized in double-blind manner to receive warfarin (target international normalized ratio [INR] 2.0 to 2.5) or placebo in addition to aspirin (150 mg daily), Changes in the culprit lesion were assessed by quantitative angiography in 50 patients after 10 weeks of therapy or after a clinical event, Progression of the culprit lesion was defined as a decrease in minimal lumen diameter >0.4 mm or a new total occlusion. Regression was defined as an increase in minimal lumen diameter >0.4 mm, Results, In subjects randomized to receive warfarin, the culprit lesion was less likely to progress (1 [4%] vs, 8 [33%]) and more likely to regress (5[19%] vs, 2[9%]) than in subjects receiving placebo (p = 0.02), Recurrent MI or a new occlusion at angiography occurred in 2 (7%) of 29 patients receiving warfarin versus 11 (39%) of 28 patients receiving placebo (p = 0.005), Conclusions, In patients with an acute coronary syndrome, combined therapy with aspirin and warfarin with a target INR of 2.0 to 2.5 for 10 weeks reduces the risk of progression or reocclusion of the culprit coronary lesion. (C) 1997 by the American College of Cardiology.