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Background: The continuation of long-term warfarin therapy is gaining acceptance in minor surgeries but maintaining therapeutic international normalized ratio (INR) values among patients during major orthopedic procedures raises concern. While bridging therapy with low-molecular-weight heparin is currently recommended for patients receiving anticoagulation, few studies have evaluated the safety of continuing warfarin during total joint arthroplasty. This study evaluated the safety and efficacy of continuous warfarin anticoagulation through total joint arthroplasty with and without prophylactic tranexamic acid (TXA)., Materials and Methods: We conducted a retrospective, matched-pair analysis of two experimental groups of patients who underwent primary total hip arthroplasty or total knee arthroplasty performed by a single surgeon. Our first experimental group, warfarin plus TXA (warfarin+TXA), consisted of 21 patients who underwent arthroplasty while receiving therapeutic anticoagulation with warfarin (INR, 2.0-3.0) and who received prophylactic TXA. Our second experimental group, warfarin without TXA (warfarin-TXA), consisted of 40 patients who underwent arthroplasty while receiving therapeutic anticoagulation with warfarin (INR, 2.0-3.0) without prophylactic TXA., Results: The percent change in hemoglobin value after surgery, red blood cells transfused, surgical site infections, bleeding complications, and thrombotic complications were similar between both experimental and control groups. When comparing the historical group with the warfarin+TXA group, the addition of TXA resulted in a statistical decrease in mean red blood cells transfused and estimated blood loss, with no statistically significant increase in complications., Conclusion: Many factors must be considered when choosing perioperative thromboembolic prophylaxis for arthroplasty candidates with medical comorbidities requiring long-term anticoagulation. This study presents data indicating that it could be safe and effective to continue therapeutic warfarin while using prophylactic TXA. [ Orthopedics . 202x;4x(x):xx-xx.].