OBJECTIVE: A publicly funded, universal infant pentavalent rotavirus vaccine (RV5) program was implemented in Queensland, Australia, in mid-2007. We sought to assess vaccine effectiveness (VE) of 3 doses of RV5 at preventing rotavirus and nonrotavirus acute gastroenteritis (AGE) hospitalizations in the first birth cohort and impact on hospitalizations in all age groups. METHODS: Hospitalization rates for rotavirus and nonrotavirus AGE in all age groups before and after RV5 introduction were compared. Population vaccine coverage, hospitalization data, and individual vaccination status were obtained from routinely collected, publicly funded state- and nationally based data sets. Data linkage was performed to calculate 3-dose VE for preventing hospitalization in the eligible age group. RESULTS: RV5 coverage in the first eligible birth cohort was 89.6% for at least 1 dose and 73.1% for 3 doses. Three-dose VE for preventing nonrotavirus AGE hospitalization was 62.3% to 63.9% (any/primary diagnosis) and 89.3% to 93.9% (any/primary diagnosis) for rotavirus hospitalizations. After program implementation, there were immediate and sustained reductions in rotavirus hospitalizations for those who were younger than 20 years and nonrotavirus AGE-coded hospitalizations for those who were younger than 5 years. CONCLUSIONS: RV5 is highly effective at preventing rotavirus hospitalizations in a developed country setting, confirming efficacy figures from the pivotal clinical trial. Additional direct and indirect effects are substantial and include reductions in nonrotavirus AGE hospitalizations in vaccinated age groups and rotavirus and nonrotavirus AGE hospitalization rates in older age groups.