The introduction of replacement therapy in the 1960s has improved medical and social circumstances gradually. The availability of prophylactic treatment has further increased the possibilities of a "normal" life for patients with hemophilia. We examined whether social participation and health-related quality of life (HRQol) of today's hemophilia patients differs from the general male population. There were a total of 721 participants in the Hemophilia in the Netherlands 5 study (HiN-5 study) ages 16 to 64 years. Patients with severe hemophilia participated less in full-time work compared with the general population. Occupational disability was reported by 35% of patients with severe hemophilia between ages 31 and 64 years, compared with 9% in the general population. HRQol of patients with severe hemophilia between ages 31 and 64 years was lower than of the general population. The differences with the general population in HRQol were least pronounced for patients between ages 16 and 30 years. Despite major improvements in treatment during the last decades, patients with hemophilia are still less involved in full-time paid work and suffer more from occupational disability than men from the general population. After the introduction of prophylactic treatment, the number of patients who are occupationally disabled is reduced.