Benefits of bypassing agents for maintaining haemostasis in major surgeries have been described in the literature; however, their use has a substantial economic impact. This study assessed the cost of FEIBA, an activated prothrombin complex concentrate and recombinant factor VIIa (rFVIIa) when used in inhibitor patients undergoing major surgeries. After reviewing published literature, a cost minimization model was developed describing dosing regimens recommended and used during major surgeries for FEIBA (pre-operative: 75-100 U kg(-1); postoperative: 75-100 U kg(-1) q 8-12 h days 1-5 and 75-100 U kg(-1) q 12 h days 6-14) and rFVIIa (pre-operative: 90 microg kg(-1); intra-operative: 90 microg kg(-1) q 2 h; postoperative: 90 microg kg(-1) q 2-4 h days 1-5 and 90 microg kg(-1) q 6 h days 6-14). Using a 75 kg patient and US prices, total drug cost was calculated for three scenarios: use of FEIBA or rFVIIa alone and a third case combining rFVIIa pre- and intra-operative and FEIBA throughout a 14-day postoperative period. Dosage amounts of modelled bypassing agents were similar to cases in the literature. Using FEIBA instead of rFVIIa would decrease total drug cost by >50% and save over $400,000 per surgery. Sequential use of both bypassing agents would increase total drug cost by 9% when compared with FEIBA alone, but would remain >40% lower than rFVIIa alone. Univariate sensitivity analyses confirmed robustness of results. As large amounts of bypassing agents are necessary for patients with inhibitors to undergo major surgeries, cost is a major consideration. Use of FEIBA alone or in combination with rFVIIa has emerged as a cost-saving approach.