OBJECTIVES: To evaluate the current utilization, effectiveness, and safety of antithrombotics for preventing deep vein thrombosis (DVT) after major orthopedic surgeries. METHODS: This one-year retrospective cohort study was conducted at a medical center in Taiwan from January 1st to December 31thin 2011. Adult patients (above 18 years) who had undergone total hip replacement or total knee replacement were identified by inpatient electronic database. Medical records were reviewed from the surgery day to at least three months post-operation for collecting demographic details and DVT-related clinical symptoms as the surrogate of effectiveness. Demographic and prescribing patterns of antithrombotics were assessed by descriptive statistic. Relative risk (RR) was calculated with 95% confidence interval (95%CI). RESULTS: Medical records of 212 patients (66.98% women) were reviewed. A total of 81 patients (38.21%) received rivaroxaban, 37 patients (17.45 %) received aspirin, 7 patients (3.30%) received warfarin, and 45 (21.22%) patients received no antithrombotics and antiplatlets. There was no stroke case in aspirin, warfarin, and aspirin/rivaroxaben combination group. Compared to other antithrombotics, rivaroxaben was associated with higher RR for stroke (RR 1.11, 95%CI 0.10-11.92), but lower RR for bleeding (RR 0.83, 95%CI 0.32-2.19). However, aspirin/rivaroxaben combination group showed an increase in bleeding events (RR 1.87, 95%CI 0.46-7.70). CONCLUSIONS: Treatment with aspirin or warfarin seems effectively reduce the risk of stroke. Aspirin/rivaroxaben combination may increase bleeding events. Further studies are needed to explore the effectiveness and safety of antithrombotics using a longitudinal data source with sufficient patients’ characteristic data.