Summary. Background: Clotting factor products have been safe for HIV since 1985, and for hepatitis C since 1992. Few studies have reported on mortality in the total population of hemophilia patients after the period of risk of viral infection transmission. Objectives: We studied the mortality, causes of death, and life expectancy of hemophilia patients between 1992 and 2001. We compared these findings with those of previous cohorts, together spanning the periods before, during, and after the use of potentially contaminated clotting products. Patients and methods: We performed a prospective cohort study among 967 patients with hemophilia A and B. Death rates, overall and cause-specific, were compared with national mortality figures for males adjusted for age and calendar period as standardized mortality ratio (SMRs). Results: Between 1992 and 2001, 94 (9.7%) patients had died and two patients were lost to follow-up (0.2%). Mortality was 2.3-times higher in hemophilia patients than in the general male population (SMR 2.3 95% confidence interval 1.9–2.8). In patients with severe hemophilia, life expectancy decreased from 63 (1972–1985) to 59 years (1992–2001). Exclusion of virus-related deaths resulted in a life expectancy at birth of 72 years. Conclusions: AIDS was the main cause of death (26%) and 22% of deaths were because of hepatitis C. In patients not affected by viral infections, there still appeared to be a trend toward a moderately increased mortality compared with the Dutch male population. Thus, mortality of patients with hemophilia is still increased; this is largely because of the consequences of viral infections.