OBJECTIVES: Hemophilia A is rare bleeding disorder where patients have defective or deficient levels of coagulation factor VIII (FVIII). Recombinant FVIIII (rFVIII) are manufactured to treat the patients, either as a full-length rFVIII (FL-rFVIII) molecule replicating natural human FVIII or with the B-domain deleted (BDD-rFVIII). It has been suggested that Deletion of B domain had been implemented to improve production profitability. However, this deletion has been shown to induce increase factor consumption by 32.8% in the US (Epstein 2011) and also may increase the risk of developing inhibitors for previously treated patients (PTP) Hazard Ratio=10.8 (Aledort 2011). Both differences can have an important impact on patient health and on the national healthcare budget. METHODS: A Excel-based decision tree model had been developed to compare the overall cost to treat severe haemophilia A patients from a healthcare system perspective with the most used FL-rFVIII and BDD-rFVIII in Europe. Clinical data are from the published literature. Pharmacy cost of rFVIII, immune tolerance induction (ITI) and bypassing agents for patients who developed inhibitors are considered from French healthcare perspective. RESULTS: Both products are listed and reimbursed at similar unit price whereas the overall cost to treat a patient with BDD-rFVIII is higher considering the increased consumption on prophylaxis and the risk of developing an inhibitor for PTPs. This may be translated into an increase cost of 36% over 1 year and 40% over 3 years when treating children and adult PTPs with prophylaxis. CONCLUSIONS: The cost study confirms the cost advantage of rFVIII (FL-rFVIII) as well as the need to compare the rFVIII based on the overall cost and not on the price per unit.