OBJECTIVES: A US hospital-based economic model was developed to quantify the potential cost savings associated with use of an improved non-immunogenic bypassing agent with faster bleeding resolution, sustained control and a reduced need for retreatment in order to estimates the inpatient costs for on-demand treatment of bleeds of haemophilia patients with inhibitors. METHODS:  An Excel-based model patterned the inpatient care associated with use of currently available bypassing agents: plasma-derived activated prothrombin complex concentrate (pd-aPCC) and recombinant Factor VIIa (rFVIIa). We used the model to simulate the potential impact of faster bleeding resolution associated with an improved bypass agent by examining a realistic range of theoretical improvements to the rFVIIa profile. The model was parameterized with treatment-specific average resource use, service and pharmacy costs, and source admission estimates based on a retrospective analysis of the Premier Perspective™ Database, including 1218 inpatient stays with an ICD-9 diagnosis of hemophilia A that were identified from 2003-2008. All costs are reported in 2008 USD. RESULTS: In the baseline analysis, the average per-patient costs associated with the inpatient treatment of hemophilia with inhibitors were slightly lower with rFVIIa as compared with pd-aPCC ($78,086 vs. $78,141). The observed cost difference was attributable to an observed difference in the percentage of inpatient stays where the patient was admitted through the ER associated (rFVIIa: 54%; pd-aPCC: 80%). Exploratory sensitivity analyses showed that a potentially faster-acting non-immunogenic treatment (e.g., 10% reduction in length of stay per patient admittance and a 10% reduction in average duration of bypass agent therapy per patient admittance) could impart appreciable incremental cost savings of $7867 (10.1%) compared with pd-aPCC treatment.   CONCLUSIONS: Our analysis showed that the availability of more effective bypassing agents with faster bleed resolution may have the potential to confer significant inpatient cost savings through reductions in length of stay and duration of bypass agent treatment.