To estimate the effectiveness of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for protecting people in a largely coronavirus disease 2019 (COVID-19)-naïve regional population from hospitalisation with symptomatic COVID-19. Retrospective cohort study; analysis of positive SARS-CoV-2 polymerase chain reaction (PCR) test results linked with Central Queensland hospitals admissions data and Australian Immunisation Register data. Adult residents of Central Queensland, 1 January - 31 March 2022. Vaccine effectiveness (1 - relative risk of hospitalisation for vaccinated and unvaccinated people) with respect to protecting against hospitalisation with symptomatic COVID-19 after primary vaccination course only (two doses of an approved SARS-CoV-2 vaccine) and after a booster vaccine dose. Positive SARS-CoV-2 test results were recorded during 1 January - 31 March 2022 for 9682 adults, 7244 of whom had been vaccinated (75%); 5929 people were aged 40 years or younger (62%), 5180 were women (52%). Forty-seven people were admitted to hospital with COVID-19 (0.48%), four required intensive care (0.04%); there were no in-hospital deaths. Vaccine effectiveness was 69.9% (95% confidence interval [CI], 44.3-83.8%) for people who had received only a primary vaccination course and 81.8% (95% CI, 39.5-94.5%) for people who had also received a booster. Of the 665 Aboriginal and Torres Strait Islander adults with positive SARS-CoV-2 test results, 401 had been vaccinated (60%). Six Indigenous people were hospitalised with symptomatic COVID-19 (0.9%); vaccine effectiveness was 69.4% (95% CI, -56.5% to 95.8%) for Indigenous people who had received a primary vaccination course only or the primary course and a booster. The hospitalisation rate for Central Queensland people with PCR-confirmed Omicron variant SARS-CoV-2 infections during the first quarter of 2022 was low, indicating the protection afforded by vaccination and the value of booster vaccine doses.