Key PointsQuestionIs aspirin monotherapy more effective than enoxaparin in preventing mortality within 90 days following hip or knee arthroplasty procedures when either drug is used for venous thromboembolism (VTE) prophylaxis?FindingsIn this secondary analysis from a cluster randomized, crossover trial that included 23 458 patients, there was no significant difference found in mortality within 90 days for patients allocated to aspirin compared with patients allocated to receive enoxaparin for VTE prophylaxis.MeaningThis secondary analysis of cluster randomized crossover trial found that in patients undergoing hip or knee arthroplasty procedures, aspirin was not associated with a lower mortality rate within 90 days of surgery compared with enoxaparin.