OBJECTIVES: Hemophilia B is a genetic disease characterized by a defect in coagulation factor IX, needed for this function. Moderate hemophilia is defined as a blood clotting factor level from 1 to 5 % of normal, some people from this group, can have bleeding similar to people with severe hemophilia; most of them, has one bleeding episode monthly. This analysis is aimed to estimate the cost-effectiveness of prophylactic treatment of moderate hemophilia B, compared to on demand treatment in Colombia. METHODS: A decision tree model was developed using a time horizon of life expectancy. A societal perspective was adopted, and an annual discount rate of 3% was applied to costs and effectiveness measures. Prophylactic treatment with recombinant factor IX (25 IU/kg 3 times per week) was compared to on demand treatment (40 IU/kg BID for 4.5 days for each bleeding episode). Simulation of base case was applied for a patient of 10 years, weight of 37 kg without inhibitors. Effectiveness and probabilities of adverse events were taken from a literature. Costs (direct and indirect) were taken from local tariff manuals (SOAT and SISMED). Costs are presented in 2013 US$ (1$ USD = $ 1 927 COP). Effectiveness measures were number of cases avoided of bleeding, hemarthrosis and arthropathy. All data were validated with a clinical expert. Univariate sensitivity analysis was done. RESULTS: Over the time horizon, prophylactic treatment avoids 275 episodes of bleeding and 23 of joint damage. Total expected costs with prophylactic treatment were US$ 7.4M compared to on demand treatment US$ 8.2M, generating savings of US$ 870,778. Sensitivity analysis showed the robustness of the results (99.3 % dominant) CONCLUSIONS: Prophylactic treatment of moderate hemophilia B, with recombinant factor IX would be a cost-saving intervention from the social perspective.