OBJECTIVES: Patients with hemophilia A and inhibitors are at high risk for severe bleeding and progression of joint disease with consequent deterioration of their health-related quality of life (HRQoL). The Pro-Feiba Study was designed to assess clinical and quality of live outcomes comparing prophylaxis to on demand therapy.  METHODS: A prospective, randomized, crossover study (Pro-FEIBA Study) aimed  to evaluate safety, efficacy  and HRQol of AICC for bleeding prophylaxis in hemophilia A patients >2 years with high-responding inhibitors. The study compared 6 months of AICC prophylactically dosed at 85 U/kg ±15% on 3 non-consecutive days per week with 6 months of on-demand therapy (85 U/kg ±15%). The 2 study periods were separated by a 3-month washout (patients used on-demand therapy). Quality of life in patients >14 years was assessed at the beginning and end of each study period with 2 generic instruments: the Short-Form 36 (SF-36) and the EQ-5D. RESULTS: Nineteen subjects, of 26 valid patients , were >14 years and potentially evaluable for HR-QoL. Of these, 18 patients (mean age: 32.6 years; min-max: 16.1-62.8) completed SF-36 and/or EQ-5D questionnaires at each time point. Sixteen patients completed both the SF-36 and the EQ-5D at the beginning and end of each study period, 1 patient completed only the SF-36, and 1 patient completed only the EQ-5D. A comparison of the 2 periods showed a trend towards HRQoL improvement favouring prophylaxis. Differences between the 2 study period for SF-36 physical component summary (PCS) were statistically significant in “good responders” (≥50% bleeding episodes reduction) (p=0.018). PCS differences were statistically significant in all evaluable subjects when measured before and after prophylaxis (p=0.047). The EQ-5D health profile showed an improvement trend toward prophylaxis.  CONCLUSIONS: AICC prophylaxis significantly improved HRQoL as compared with episodic treatment. Larger cohorts and longer follow-up are necessary to confirm these data.