OBJECTIVES: We evaluated Health-Related Quality of Life (HR-QoL) in hemophilia people with inhibitors and investigated if QoL is associated to patients’ clinical status. METHODS: The COCIS (Cost Of Care of Inhibitors) study was a longitudinal study involving 52 hemophiliacs (median age 35, 15-64) with inhibitors, 98% high responders, sequentially enrolled at 11 Italian Hemophilia Care Centers. Information on demographics, clinical status, health-care resources consumption was prospectively collected. QoL was investigated by means of the generic instruments EQ-5D and SF-36. RESULTS: With the EQ-profile the majority of patients reported some/moderate problems in domains “pain/discomfort” (72%), “mobility” (66%) and “usual activities” (54%). Around one third declared some/moderate problems with “anxiety/depression” (34%) and “self-care” (32%). No more than 6% of patients reported severe problems in any of the domains. The EQ-Visual Analogue Scale (VAS), measuring the global health state perception, was normally distributed, with a median value of 66 (30-95). The SF-Mental Component Summary (MCS) had a median value of 52.8 (15.5 – 68.1), while the SF-Physical Component Summary (PCS) had a median value of 35.2 (15.2 – 55.0). A strong association was found between orthopedic status and global HR-QoL (EQ-VAS, Pearson’s r=0.56, p<0.01). In particular, the physical component of HR-QoL was the most influenced by the patients’ orthopedic status (Physical Component Summary, Pearson’s r=- 0.359, p<0.01). Other clinical parameters, in particular inhibitor titers and bleeding frequency, were not associated with patients’ HR-QoL. CONCLUSIONS: Modern health care strategies aimed at treating or, better, at preventing hemophilic arthropathy should be considered to improve quality of life in inhibitor patients.