OBJECTIVES To assess the cost effectiveness of rivaroxaban against enoxaparin for the prevention of venous thromboembolism (VTE) in patients undergoing total hip replacement (THR) or total knee replacement (TKR) in a Colombian setting. METHODS A cost-effectiveness model was developed to assess the cost effectiveness of rivaroxaban compared to enoxaparin in a Colombian setting over a 5-years time horizon. The model was divided into three modules: prophylaxis, post-prophylaxis, and long-term complications. The first two modules constitute the acute phase and were represented in a decision tree while the long-term complications module was developed as a Markov process. Efficacy and safety parameters used in the prophylaxis module were derived from the RECORD trials in the prevention of VTE following THR or TKR. Published epidemiological and clinical data were used to estimate the risk of VTE and other long term complications beyond the trial period. The analysis was performed from a healthcare payer's perspective. Cost data was based on clinical guidelines, product labels, nationally and locally published sources, and expert opinion. VTE related utilities reported in literature were used in this analysis. One-way and probabilistic sensitivity analyses were performed in order to address uncertainty around the model inputs. RESULTS Rivaroxaban dominated enoxaparin, yielding improved health outcomes (QALYs) and savings of COP 114,345 per patient in THR. Savings were driven mainly by reduced outpatient administration costs. Rivaroxaban also dominated enoxaparin with savings of 152,484 COP in TKR patients. Probabilistic sensitivity analyses showed dominance in 89% of cases in THR and in 99% in TKR. CONCLUSIONS Rivaroxaban is a cost-effective alternative to enoxaparin for the prevention of VTE following THR or TKR in Colombia.