OBJECTIVES: The development of inhibitors is the most challenging complication of hemophilia treatment. Bypassing agents (i.e. aPCC and rFVIIa) remain the therapy of choice but account for a significant proportion of treatment cost. This study aims to compare the cost-effectiveness of aPCC vs. rFVIIa in on-demand treatment from the Brazilian public health system perspective.  METHODS: A literature based cost model was developed based on utilization and efficacy (evaluated at 2, 6, 12, 24, 36 and 48 hours after infusion) data from the FENOC (head-to-head) trial which investigated the equivalency of the clinical efficacy of aPCC and rFVIIa in on-demand treatment. The median (range) treatment dose was 84.6 (51.5-100) U/kg and 212.5 (98.6-261.8) µg/kg for aPCC and rFVIIa, respectively. Hemostatic efficacy ranged from 75% to 97.6% for aPCC and 60.4% to 85.4% for rFVIIa. Bleed resolution rate also ranged from 53.2% to 95.1% for aPCC and 38.3% to 92.7% for rFVIIa. Cost analysis was limited to drug costs and prices were obtained from the 2014 Brazilian Official Diary: U$0.71/U and U$0.64/µg for aPCC and rFVIIa, respectively. One-way sensitivity analyses were performed to determine model robustness when dose and price were varied by ±25%.  RESULTS: The cost/kg per on-demand bleed treatment was 55.9% lower for aPCC compared to rFVIIa. The cost/kg per treatment efficacy was 64% to 79% lower for aPCC compared to rFVIIa. Similarly, cost/kg per resolved bleed was 68% to 81% lower for aPCC compared to rFVIIa. Results remained robust for all one-way sensitivity analyses conducted. Given, an estimated total inhibitor population of 684 in Brazil, total saving with aPCC can vary from U$13.2-U$53.2 million depending on market share.  CONCLUSIONS: aPCC was the dominant therapy in on-demand treatment. Using the current Brazilian prices, for each bleed treated with rFVIIa about 2.3 bleeds could be treated with aPCC at comparable cost.