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Introduction: Venous thromboembolism (VTE) is a known complication of major orthopedic surgery. Although guidelines now allow the use of aspirin as an alternative to anticoagulants as VTE prophylaxis after knee or hip arthroplasty, there is limited data on contemporary use and outcomes with aspirin. We conducted a retrospective cohort study to describe antithrombotic agents used after knee and hip arthroplasty and post-operative VTE outcomes.Hypothesis: We assessed the hypothesis that VTE prevention with aspirin was not related to an increased risk of postoperative VTE after knee or hip arthroplasty compared to anticoagulation.Methods: We used data from MedAssets, which is an administrative database containing billing details on the patient-level from about 400 hospitals in the U.S., and included all adults with a principal hospital discharge diagnosis of knee or hip arthroplasty based on International Classification of Diseases, 9th edition (ICD-9) codes between January 1, 2013, and December 31, 2014. We identified charges for medications used for VTE prophylaxis within 7 days after the index surgery. The primary outcome was postoperative VTE, identified by searching for VTE-specific ICD-9 codes from the index hospitalization, rehospitalization within 30 days, or during an outpatient visit within 90 days. We compared postoperative VTE risk between patients receiving aspirin-only and those receiving anticoagulants using propensity score-adjusted multivariable logistic regression models adjusted for VTE risk factors, hospital characteristics and length of stay.Results: We identified 74,234 patients who underwent knee arthroplasty and 36,192 with hip arthroplasty who received pharmacologic VTE prophylaxis. The most common post-operative anticoagulant medications were warfarin (25.2%; 27,850 of 110,426) and enoxaparin (24.1%; 26,560 of 110,426). Aspirin was used as the sole agent in 27.0% (20,047 of 74,234) of knee and 29.8% (10,769 of 36,192) of hip arthroplasties. Patients receiving only aspirin were younger and had fewer comorbidities compared to those who received anticoagulants. Postoperative VTE events occurred in 495 of 74,234 (0.67%) patients undergoing knee arthroplasty and 145 of 36,192 (0.40%) undergoing hip arthroplasty. Patients who received only aspirin after surgery did not have a higher risk for postoperative VTE compared to patients who received anticoagulants: adjusted odds ratio 0.92; 95% CI, 0.61-1.39 for knee and adjusted odds ratio 0.73; 95% CI, 0.56-0.95 for hip arthroplasty.Conclusions: In conclusion, aspirin was the most frequently administered individual antithrombotic agent in a large contemporary sample of U.S. patients undergoing knee or hip arthroplasty. Postoperative VTE prophylaxis with aspirin-only may be a safe option in this population and was not associated with a higher risk of postoperative VTE compared to anticoagulants.