Background: It is estimated that annually 300000 cases of rotavirus-induced gastroenteritis (RVGE) occur in children aged up to 5 years in France. A two-dose vaccine against rotavirus infection (RIX4414; Rotarix™, GlaxoSmithKline), has been shown to be highly effective against severe RVGE. Objective: This study evaluated the cost effectiveness of general vaccination against rotavirus using RIX4414 in France. Methods: A Markov model simulated RVGE events and the associated outcomes and costs relating to general vaccination of infants against rotavirus infection using RIX4414 (Rotarix™) in a birth cohort of children aged up to 5 years in France with a combined adjustment for age distribution with the seasonality of the infection. Costs and outcomes were estimated from a limited societal perspective, including direct medical costs paid out of pocket or by third-party payers, as well as the proportion of direct medical costs reimbursed by the health authorities. Indirect costs were not included in the base-case analysis. The primary outcome measure was the incremental cost per QALY. Results: Vaccination with RIX4414 incurred an incremental cost of €44583 per QALY at a public price of €57 per vaccine dose. Univariate sensitivity analyses showed that the parameters with the largest influence on the results were the transition probabilities of severe diarrhoea, seeking medical advice and emergency visits, utility scores of diarrhoea (mild) in children and infants, and the discount rate for benefits. Probabilistic multivariate sensitivity analysis confirmed these results. The acceptability curve indicated that 94% of the results were under an informal threshold of €50000 per QALY. Comparing our results with those of a recently published study using pooled data for two rotavirus vaccine products in France, the main differences are explained by differences in model structure and in data input values. They include a different age distribution of the infection, shorter duration of the at-risk period (3 years instead of 5 years), different vaccine efficacy, different unit cost data, different disease duration, and different disutility values for the health states in the model. There is a need for agreed standards to improve comparability of results from different studies. Conclusions: The results demonstrate that a generalized vaccination strategy with RIX4414 would be cost effective in France from a limited societal perspective, depending on the baseline assumptions for disease progression and on utility scores selected.