In an attempt to improve upon the reported long-term patency rates of 65% to 85% for saphenous vein coronary artery bypass grafts (CABG), a prospective randomized trial comparing warfarin, aspirin, and placebo treatment in post-CABG patients was carried out. From an initial group of 216 patients, 161 patients remained in the study, and vein graft patency was determined in 111 patients (220 grafts) from 1 to 47 months postoperatively. There was a trend toward better cumulative graft patency in patients given warfarin, but the results did not achieve statistical significance. Improved results with warfarin were most marked among patients who were restudied within 24 months of CABG operation, in most instances because of the development of recurrent angina pectoris. There were four major bleeding complications of warfarin therapy, including one death, over 2,108 patient-months. Since most of the occlusive changes in vein grafts appear in the first 6 to 12 months, any effect of antithrombotic therapy will be most evident in the early postoperative period, with greatly reduced impact with long-term administration. Results of this study suggest that short-term antithrombotic therapy deserves further assessment in prevention of vein graft occlusion in the first year or two following a CABG operation. This potential benefit must be evaluated in the context of the recognized bleeding complications of warfarin therapy.