OBJECTIVES: . Due to the aging of the population, musculoskeletal diseases, particularly articular diseases and fragility fractures, have been constantly increasing.  For this reason, total hip replacement (THR) and total knee replacement (TKR) have also increased. These procedures impact the quality of life and imply high risk of venous thromboembolism (VeT). VeT events have a high mortality in the elderly, 21% on hospitalized patients and up to 39% one year after the surgery. Prophylaxis for VeT is as a major strategy to minimize the consequences on patients undergoing TKR and THR. The aim of this study was to assess the cost-effectiveness (CE) of apixaban against dabigatran, rivaroxaban, fondaparinux, and enoxaparin for VeT prevention on these patients in Guatemala, from the private healthcare perspective.  METHODS: . A simulated cohort of 1,000 patients subjected to THR/TKR entered a decision-tree model to compare costs and effectiveness of apixaban (2.5 mg/12 hours), dabigatran (220 mg/day), rivaroxaban (10 mg/day), fondaparinux (2.5 mg/day) and enoxaparin (30 mg/12 hours). Effectiveness measures were: total VeT events, bleeding rates and deaths. The model used a 5 year time horizon and only direct medical costs were considered (inpatient costs, medication expenses, adverse events, tests). Effectiveness and epidemiologic data were retrieved from published literature.  Local costs (2012 US$) were gathered from the 3 private hospitals of Guatemala official databases. RESULTS: . The total VeT events were 69 for Apixaban, 55 for Rivaroxaban, 112 for Dabigatran, 86 for Enoxaparin and 45 for Fondoparinux. The estimated bleeds were 71 (Apixaban), 85 (Rivaroxaban), 85 (Dabigatran), 73 (Enoxaparin) and 31 (Fondaparinux). Apixaban dominated enoxaparin and dabigatran while rivaroxaban and fondaparinux had an ICER of US$104,177/QALY and US$103,933/QALY, respectively. In the acceptability curves, Apixaban appeared with the highest probability of being cost-effective. CONCLUSIONS: . Apixaban resulted as the cost-effective therapy for VeT prevention for adult patients in Costa Rica.