OBJECTIVES: The World Health Organisation (WHO) Guide to Identify the Economic Consequences of Disease and Injury described the financial burden of poor health for government both in terms of increased transfer costs and lost tax revenue due to reduced productivity. To evaluate the broader consequences of rotavirus we developed a quantitative “government perspective” framework to evaluate immunisation costs in Ghana. METHODS: Methods from generational accounting, human capital economics and epidemiologic modelling were combined to estimate the benefits of rotavirus vaccination in terms of measures used in financial analyses such as the Net Present Value (NPV) and Return on Investment (ROI). Data from the published literature and national statistical sources were collected. Single and multiple cohort models were developed simulating survival, direct medical costs and average lifetime fiscal transfers between the government and individuals with and without the vaccination until the age of 65 years. Direct and indirect tax rates were linked to differences in lifetime age-specific earnings to quantify the tax revenue associated with vaccinated and unvaccinated individuals. RESULTS: From a “government perspective” the results showed that every dollar invested on vaccination against rotavirus, may yield a discounted gross tax ROI equal to $2.9 and a net tax ROI of $0.55. The vaccinated and unvaccinated cohorts resulted in total lifetime discounted net tax of -$167 million -$174 million, for the vaccinated and unvaccinated cohorts, respectively. The results suggested a net fiscal benefit of approximately $7million and $54 million for the single and multiple birth cohorts, respectively. CONCLUSIONS: Vaccinating against rotavirus may result in considerable fiscal benefits. Investments in vaccinations may influence future government tax revenue and thus contribute to the sustainability of tax-financed health systems, public finances and economic growth. Estimating the broader economic impact of vaccines using the “government perspective” framework may inform cross-sectoral governmental resource allocation decisions.