Objective: To assess and compare the costs and effectiveness of different vaccination strategies against hepatitis B in Switzerland. Design: A birth cohort of 85 000 individuals was followed over their lifetime, using a decision-tree analysis. Published data were used to simulate the risk of hepatitis B virus (HBV) infection in the cohort, the consecutive clinical outcomes and the associated costs. Five new vaccination scenarios were assessed and compared with a baseline strategy of vaccination of high-risk groups. The 5 new vaccination scenarios were: (i) systematic prenatal screening and vaccination of newborns at risk; (ii) universal vaccination of infants; (iii) universal vaccination of school children; (iv) universal vaccination of infants and school children; and (v) universal vaccination of infants, school children and adolescents. Results: The incremental cost per year of life saved for systematic prenatal screening and vaccination of newborns at risk compared with the baseline scenario was estimated to be 23 350 Swiss francs (SwF; 1996 values). The 4 universal vaccination scenarios had a much larger impact on the number of chronic infections and deaths prevented. The incremental cost per year of life saved for universal vaccination compared with systematic prenatal screening and vaccination of newborns at risk ranged from SwF6120 (infant vaccination strategy) to SwF10 200 (school children vaccination strategy). In the sensitivity analysis, prevalence, vaccine price and discount rate were key elements. Conclusion: Incremental cost-effectiveness ratios are lower with universal vaccination strategies than with selective vaccination. Furthermore, with universal vaccination strategies, increasingly ambitious strategies result in higher costs but also in more incremental years of life saved.[Authors]