Background Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued.Aspirin may be effective in preventing a recurrence of venous thromboembolism.Methods We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin,at a dose of 100 mg daily,or placebo for up to 4 years.The primary outcome was a recurrence of venous thromboembolism.Results During a median follow-up period of 37.2 months,venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin(a rate of 6.5% per year vs.4.8% per year;hazard ratio with aspirin,0.74;95% confidence interval [CI],0.52 to 1.05;P = 0.09).Aspirin reduced the rate of the two prespecified secondary composite outcomes:the rate of venous thromboembolism,myocardial infarction,stroke,or cardiovascular death was reduced by 34%(a rate of 8.0% per year with placebo vs.5.2% per year with aspirin;hazard ratio with aspirin,0.66;95% CI,0.48 to 0.92;P = 0.01),and the rate of venous thromboembolism,myocardial infarction,stroke,major bleeding,or death from any cause was reduced by 33%(hazard ratio,0.67;95% CI,0.49 to 0.91;P = 0.01).There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes(rate of 0.6% per year with placebo vs.1.1% per year with aspirin,P = 0.22) or serious adverse events.Conclusions In this study,aspirin,as compared with placebo,did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events,with improved net clinical benefit.These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism. Background Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism. Methods We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism. Results during a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P = 0.09) .Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rat e of 8.0% per year with placebo vs.5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P = 0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding or or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P = 0.01). There was no significant between- group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs.1.1% per year with aspirin, P = 0.22) or serious adverse events. Confc In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism.