Indigenous children living in arid Central Australia experience frequent outbreaks of rotavirus gastroenteritis. A widespread outbreak of G9 rotavirus infection occurred several months after introduction of the RIX4414 rotavirus vaccine. We performed a retrospective case-control study to determine vaccine efficacy during the outbreak. Two doses provided an estimated vaccine efficacy of 77.7% (95% confidence interval, 40.2%-91.7%) against hospitalization for gastroenteritis. Vaccine efficacy was 84.5% (95% confidence interval, 23.4%-96.9%) against confirmed cases of rotavirus infection. Vaccination was effective in this high-burden setting.