Rotavirus infections are the leading cause of severe acute diarrhea in children. Two new rotavirus vaccines received marketing authorization in Europe in 2006. The objective of this study was to determine the epidemiological impact and cost-effectiveness of potentially incorporating rotavirus vaccination for infants into the French vaccination schedule. A decision-tree model was used to simulate the occurrence of rotavirus infection in two virtual cohorts of children, followed from birth to age 3, one without vaccination and the other with vaccination. For each cohort, the incidence of acute rotavirus diarrhea was determined by age and accounted for seasonal variations. The impact of vaccination was measured by the number of cases and hospitalizations prevented, the number of life-years gained, direct medical costs from a societal perspective, the cost per prevented hospitalization, and the cost per quality-adjusted life-year (QALY) gained. In the base-case analysis, rotavirus infection is estimated to cause 182,000 episodes of acute diarrhea, 97,000 outpatient visits, 18,000 hospitalizations, and 13 deaths among children under 3 years of age in France each year. Vaccination would prevent 89,000 cases of acute diarrhea, 10,500 hospitalizations, and 8 rotavirus-related deaths per year. At 150 euros for all doses, the vaccination program would represent an additional cost of 68 million euros for the healthcare system. The cost-effectiveness of vaccination was estimated at 298,000 euros per life-year gained and 138,000 euros per QALY gained. The sensitivity analysis shows that the cost-effectiveness ratio of this strategy varies from 64,000 to 212,000 euros per QALY gained. The introduction of a vaccination program using the new rotavirus vaccines in France would have a significant impact on severe morbidity associated with this virus. However, this strategy appears to be cost-ineffective compared to generally accepted thresholds, particularly regarding vaccination strategies, unless the price of the vaccine is significantly reduced. (R.A.)