Abstract Background: Immunization in the elderly population is critical due to the high frequency of health outcomes related to COVID-19. Objectives: This study aimed to compare the effectiveness levels of COVID-19 vaccine schedules in preventing SARS-CoV-2 infection in the older adult group who received at least one booster dose. Design: Retrospective cohort study. Methods: This study evaluated 8969 adults aged 65 and over in the Sultanbeyli district of İstanbul. COVID-19 vaccination and SARS-CoV-2 polymerase chain reaction testing data between January 14, 2021 and December 2, 2022 were obtained from the National Public Health Management System. Results: The median age of participants was 71years. The vaccines were mostly administered as CoronaVac for the first and second doses (81.4% and 82.2%, respectively) and BNT162b2 for the third and fourth doses (61.8% and 73.1%, respectively). Turkovac was administered only in booster doses (third dose 0.6%, fourth dose 4.8%). The adjusted relative vaccine effectiveness (rVE) was found to be 61.8% (95% confidence interval (CI) 51.5–69.9) in two doses of inactivated vaccine and one dose of mRNA vaccine schedule compared to the homolog booster of CoronaVac primary vaccine schedule. In two booster doses receipts, the adjusted rVE was found to be 45.4% (95% CI 13.8–65.4) in three doses of inactivated and one dose mRNA vaccine schedule and 43.0% (95% CI 20.5–59.2) in two doses of inactivated and two doses of mRNA vaccines schedule compared to the two homolog boosters with CoronaVac primary vaccine schedule. Conclusion: In this study, the effectiveness of the mRNA vaccine as a booster dose was higher than that of the homologous boosters in participants receiving the CoronaVac primary series for those aged 65 and over.