OBJECTIVE: To analyze the cost-effectiveness of combined hepatitis A and B vaccination (Vacc A+B) and hepatitis B monovaccination (Vacc B) in children and adolescents. METHODS: A decision tree combined with a Markov-model was used to predict clinical and economic outcomes for three different age groups: 0-15, 1-15, and 11-15 years. The model was designed to follow an initially vaccinated age group over 30 years. The analysis took the perspective of society, i.e., direct and indirect costs were considered. Costs were discounted at 5% per year. Primary outcomes measure was the incremental cost per avoided infection of each vaccination strategy compared to no vaccination. RESULTS: The analysis indicated that for both Switzerland and Austria, Vacc A+B is more cost-effective than Vacc B in all three compared age groups. The incremental cost-effectiveness ratios of the Vacc A+B strategy for Switzerland ranged from CHF 11,070 to 12,210 (Austria ATS 61,260 to 70,270) versus CHF 24,630 to 26,520 (Austria ATS 141,750 to 159,140) for Vacc B depending on the age group. For both vaccination strategies, the most favorable cost-effectiveness ratio was obtained when vaccinating 11-15 year olds. The superior cost-effectiveness of the Vacc A+B strategy is due to a reduction in hepatitis A coupled with a modest increase in vaccination costs. In view of evidence suggesting that hepatitis A and B cases are more frequent than officially reported, these results are likely to be conservative. CONCLUSIONS: Prevention of both hepatitis A and B as compared to hepatitis B alone is cost-effective in Switzerland and Austria. When taking into consideration the low incidence of hepatitis A in both countries, combined hepatitis A and B vaccination is likely to have even greater impact in countries with a higher incidence of hepatitis A infection.