A cost-effectiveness analysis was made to determine the effectiveness of the following strategies of mass immunization with the new recombinant vaccine against the hepatitis B virus in Spain: vaccination of adolescents, newborns, both populations, and vaccination plus passive immunization of newborns of HBsAg positive mothers. Decision trees supported on Markov models with Monte Carlo simulation have been used for the calculation of costs of the disease, and a mathematical model of differential equations was used for the simulation of the potential effectiveness of vaccination. The costs considered were those associated with the vaccination and travel of subjects, diagnosis, and treatment of the disease. The results are presented as additional cost or saving per case of infection prevented. In all assumptions, results showed that the most effective strategy for mass vaccination was the combination of vaccinating all adolescents together with active and passive immunization of children born to HBsAg positive mothers.