To evaluate the outcome of immunization strategies to prevent hepatitis B virus (HBV) transmission. A decision model was used to determine the incremental effects of the following hepatitis B immunization strategies in a birth cohort receiving immunization services in the public sector: (1) prevention of perinatal HBV infection, (2) routine infant vaccination, or (3) routine adolescent vaccination. Over the lifetime of the cohort, the reduction in infections and medical and work-loss costs of HBV-related liver disease were determined for each strategy and compared with the outcome without immunization. Prevention of perinatal infection and routine infant vaccination would lower the 4.8% lifetime risk of HBV infection by at least 68%, compared with a 45% reduction for adolescent vaccination. From a societal perspective, each strategy was found to be cost saving, but was not cost saving with respect to direct medical costs. The estimated cost per year of life saved was $164 to prevent perinatal HBV infection, $1522 for infant vaccination, and $3730 for adolescent vaccination. Routine vaccination of infants in successive birth cohorts to prevent HBV transmission is cost-effective over a wide range of assumptions. While economically less attractive than infant vaccination, adolescent vaccination could serve to protect those children who were not vaccinated as infants.