OBJECTIVES: Rotavirus infection causes severe gastroenteritis in children worldwide. Its disease burden has been reduced in countries where mass rotavirus vaccination programmes have been introduced. England and Wales (E&W) have not yet implemented such a mass vaccination programme, but are currently re-evaluating its potential cost-effectiveness. Our study uses a dynamic model to predict the epidemiological and economical effect of such a mass vaccination programme in E&W beginning in the autumn of 2011. METHODS: A previously published age-structured dynamic model was upgraded and parameterised with country-specific data for the introduction of the oral rotavirus pentavalent vaccine. We report the impact of vaccination on disease incidence reduction, timing of seasonal epidemics and herd immunity levels. The model was then used to assess whether a mass vaccination of RotaTeq is cost-effective and affordable for E&W. RESULTS: Our results predict that vaccination can reduce the burden of severe disease by 70% and delay the epidemic peak by two and a half months with coverage of 95%. Our calculations further show that herd immunity accounts for about a quarter of the reduction in incidence. If the pentavalent vaccine-induced immunity does not wane over five years, severe disease in children under five years of age is eliminated within two years after the introduction of vaccination. The probability of a mass vaccination strategy being cost-effective is presented under likely vaccine waning scenarios, administration cost assumptions and possible dose prices. CONCLUSIONS:  This work allows policymakers to determine both the epidemiological impact and cost implications of a mass vaccination programme against rotavirus with the pentavalent vaccine in England and Wales. Although long considered unlikely to be cost-effective in E&W using static models, the pentavalent vaccine demonstrates a significant impact in reducing rotavirus cases at acceptable levels of cost-effectiveness when using appropriate modelling techniques.