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To evaluate the incidence and prevalence of hemophilia in Italy and the impact of HIV infection on the Italian hemophiliac population, data from a computerized national registry of patients from 95% of the hemophilia care centers in Italy were analyzed. A total of 4643 patients were included in the registry. The prevalence of hemophilia A was 8.2 per 100,000 males, with no significant regional differences; for hemophilia B the corresponding figure was 1.5 per 100,000. Temporal trends in hemophilia incidence suggest that the diagnosis of mild and moderate hemophilia has improved. The overall HIV prevalence was 26% and was significantly (p < 0.001) higher in patients with hemophilia B (47.1%) compared to those with hemophilia A (26.8%) or other diseases (16.5%). The highest rate of HIV seropositivity was among patients 20-29 years of age. The annual amount of clotting factor concentrates received was significantly (p < 0.001) higher in HIV seropositive patients than in those who were seronegative. Antibody testing was never performed on 10.1% of severely affected patients. The number of patients in the Italian registry was similar to the number that would have been expected based on prevalence estimates from other countries. In comparison with other countries, the prevalence of HIV infection recorded in Italy was lower in persons with hemophilia A, but higher in those with hemophilia B. Our study demonstrates the usefulness of a registry in delineating the epidemiology of hemophilia and in studying risk factors for HIV infection. It also underlines the need for continuing surveillance of this population.