BACKGROUND: Major adverse cardiac events (MACEs) are a common cause of death after non-cardiac surgery. Despite evidence for the benefit of aspirin for secondary prevention, it is often discontinued in the perioperative period due to the risk of bleeding. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in order to compare the effect of low-dose aspirin with that of placebo on myocardial damage, cardiovascular, and bleeding complications in high-risk patients undergoing non-cardiac surgery. Aspirin (75 mg) or placebo was given 7 days before surgery and continued until the third postoperative day. Patients were followed up for 30 days after surgery. RESULTS: A total of 220 patients were enrolled, 109 patients received aspirin and 111 received placebo. Four patients (3.7%) in the aspirin group and 10 patients (9.0%) in the placebo group had elevated troponin T levels in the postoperative period (P=0.10). Twelve patients (5.4%) had an MACE during the first 30 postoperative days. Two of these patients (1.8%) were in the aspirin group and 10 patients (9.0%) were in the placebo group (P=0.02). Treatment with aspirin resulted in a 7.2% absolute risk reduction [95% confidence interval (CI), 1.3-13%] for postoperative MACE. The relative risk reduction was 80% (95% CI, 9.2-95%). Numbers needed to treat were 14 (95% CI, 7.6-78). No significant differences in bleeding complications were seen between the two groups. CONCLUSIONS: In high-risk patients undergoing non-cardiac surgery, perioperative aspirin reduced the risk of MACE without increasing bleeding complications. However, the study was not powered to evaluate bleeding complications.