OBJECTIVES: Rotavirus (RV) is a major cause of gastroenteritis (GE) in infants but can be prevented by vaccination. The study objective was to estimate the cost effectiveness of universal rotavirus vaccination of infants from an Irish Healthcare payer perspective. METHODS: A published Markov model, calibrated to observed Irish epidemiological data was used. A cohort of 70,600 newborns was followed over five years during which the seasonality of infection and protective effects of breastfeeding were captured. Routine vaccination with the oral 2- dose vaccine RIX 4414 was compared with no vaccination. Efficacy from a European phase-III trial (102247) showed 96% and 86% against severe RVGE and 100% and 92% against hospitalisations due to RV in the first and second years post vaccination respectively. Costs were from published sources in 2007 prices. Utilities came from a UK study of physician scores using the EQ-5D questionnaire. Costs and effects, discounted at 3.5%, were assessed over lifetime. Sensitivity analyses were conducted. RESULTS: The model estimated that 14,700 GP visits, 4,000 A&E visits, 3,400 hospitalisations and 840 nosocomial cases occurred in the birth cohort at a cost of €7.3m. With a coverage rate of 87% the number of GP and hospital visits could be reduced by 82% with vaccination. Cost effectiveness was estimated at €29,398 per QALY. These results were driven by the high rate of hospitalisation due to RV. The results were most sensitive to the cost of vaccination and hospitalisations, incidence of RV and hospitalisations and the discount rate. CONCLUSIONS: Rotavirus imposes a significant financial burden on the Irish health care system. Universal vaccination of infants is a cost-effective approach to reducing this burden.