OBJECTIVES: Anti-thrombotic prophylaxis is routinely used in patients undergoing elective total hip or knee replacement (THR or TKR) to reduce the risk of venous thromboembolism (VTE). In Spain, the standard of care is enoxaparin, a low-molecular-weight heparin. Rivaroxaban (factor Xa inhibitor) 10 mg once-daily dose, a direct oral anticoagulant, demonstrated superior efficacy and similar safety profile to enoxaparin in randomized clinical trials (RECORD program). The aim of the study was to estimate the potential cost-savings from an increased use of rivaroxaban to prevent VTE in patients undergoing elective THR or TKR for the Spanish National Health System (NHS). METHODS: A budget impact model was performed considering a hypothetical scenario where rivaroxaban use was incremented with respect to enoxaparin by 10%, 20%, and 30% in 2017, 2018 and 2019 for the Spanish population undergoing THR and TKR (alternative scenario). Effectiveness data (rates of thromboembolic and major bleeding events and resources use: anesthesia and nurse care) were obtained from the Spanish cohort of the international, observational XAMOS study in routine practice. Costs (pharmacologic prophylaxis, events, anesthesia and nurse care) were estimated from the Spanish NHS perspective (Euros 2014). The annual cost was estimated based on the mean cost per patient and the estimated distribution of rivaroxaban and enoxaparin in the base case scenario and alternative scenario over the 3 years. RESULTS: The difference in cost per patient undergoing THR or TKR with rivaroxaban versus enoxaparin was -€105. The impact of increasing the use of rivaroxaban in the THR cohort, was -€206,890, -€411,413, and -€613,506 for 2017, 2018, and 2019, while in the TKR cohort, the impact was -€351,232, -€698,446, and -€1,041,533, respectively. CONCLUSIONS: The study demonstrated that rivaroxaban increased use would lead in a significant cost-savings for the Spanish NHS in the in VTE prophylaxis in patients undergoing elective THR and TKR.