BACKGROUND The efficacy of aspirin for prevention of thrombotic graft occlusion after coronary artery bypass grafting (CABG) depends both on the dosage and time window of administration. Early and late graft patency were therefore assessed in a prospective, double-blind, randomized, placebo-controlled trial of aspirin, 324 mg daily, given within 1 hour of CABG. RESULTS Angiographic graft patency was determined at 1 week (231 patients) and 1 year (219 patients) after CABG. The early vein graft occlusion rate was 1.6% on aspirin and 6.2% on placebo (p = 0.004), and late graft occlusion rate was 5.8% on continued aspirin and 11.6% on placebo (p = 0.01). New graft occlusion between 1 week and 1 year was less common in patients on aspirin than on placebo (4.3% versus 7.4%, p = 0.013). The protective effect of aspirin against occlusion persisted in most subgroups of graft type, graft flow, diameter of recipient artery, location of grafted artery, and endarterectomy. Mean chest tube blood loss for the first 24 hours was 571 ml for the aspirin group and 563 ml for the placebo group. Red cell transfusion requirements were 902 ml in the aspirin group and 934 ml in the placebo group (p = NS). The reoperation rate was 4.8% in the aspirin group and 1% in the placebo group (p = 0.1). CONCLUSIONS Immediate postoperative administration of aspirin (324 mg) improves early graft patency and, with continued usage, protects against further occlusion up to 1 year after CABG. Postoperative blood loss was similar in the two groups; however, aspirin was associated with a nonsignificant higher rate of reoperation.