OBJECTIVES: Hemophilia is a recessive genetic disease that does not allow adequate blood clotting; this is characterized by a defect in coagulation factors, needed for this function. Hemophilia B (factor IX deficiency) has a prevalence of 0.81 per 100,000 in Colombia (96% male). Severe hemophilia is defined as a blood clotting factor level ≤1%. This analysis is aimed to estimate the cost-effectiveness of prophylactic treatment of severe 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 2 times per week) was compared to on demand treatment (50 UI/kg TID for 8.5 days for each bleeding episode). A cohort of 1000 patients (age 15 - 62), with an average weight of 60kg was simulated: estimates of 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 2012 US$. Effectiveness measures were number of cases avoided of bleeding and joint damage. All data were validated with a clinical expert. Univariate sensitivity analysis was done. RESULTS: Over the time horizon evaluated, prophylactic treatment avoids 681 cases of bleeding and 246 of joint damage. Total expected costs with prophylactic treatment were US$3.86M compared to on demand treatment US$2.09M. The incremental cost effectiveness ratio (ICER) for prophylactic treatment was US$2592/avoided bleeding and US$7172/avoided joint damage (cost-effectiveness threshold:  1 Colombian GDP per capita = US$7235). Sensitivity analyses showed the robustness of the model. CONCLUSIONS: Prophylactic treatment of severe hemophilia B, with recombinant factor IX would be a highly cost-effective intervention from the social perspective.