OBJECTIVES: To assess the incremental cost-effectiveness ratios of Immune Tolerance Induction (ITI) therapy with plasma derived FVIII concentrates versus on-demand treatment with Recombinant FVIIa (rFVIIa) in hemophilia A with high titer inhibitors from Ministry of Health perspective of  Iran. METHODS: This study was based on the study of Knight et al , which evaluated the cost-effectiveness ratios of different treatment for hemophilia A with high-responding inhibitors. To adapt Knight’ Results to the Iranian context, a few clinical parameters were varied and cost data were replaced with the corresponding Iranian estimates of resource use. The time horizon of the analysis was 10 years. One-way sensitivity analyses were performed varying the cost of the clotting factor, the drug dose, and the administration frequency to test the robustness of the analysis. RESULTS: Comparison of the incremental cost-effectiveness ratios (ICERs) between the three ITI protocols and the On-Demand regimen with rFVIIa show that all three ITI protocols dominates On-Demand regimen with rFVIIa between ITI protocols the Low-Dose ITI protocol dominates both the Bonn ITI protocol and the Malmö ITI protocol, would also be preferred ITI protocol. All of three ITI protocols dominate the On-Demand strategy as they have both a lower average lifetime cost and higher QALYs gained.  The cost per QALY gained for the Bonn ITI protocol compared with the Malmö ITI protocol was $249,391.84. The cost per QALY gained for the Bonn ITI protocol compared with the Low-Dose   ITI protocol  was $842,307.69. CONCLUSIONS: The results of data derived from our study suggest that The Low-Dose ITI protocol   may be a less expensive and/or cost-effective option compared with on-demand first-line treatment with rFVIIa.