Background: We evaluated the effectiveness of the BNT162b2 vaccine against infection, symptomatic infection, and hospitalization in older people during the Delta-predominant period (July 1 to September 30, 2021).Methods: We performed a population-based cohort study in an older adult population aged ≥65 years using data from the Vaccine Effectiveness, Networking, and Universal Safety Study conducted from January 1, 2019, to September 30, 2021, in Japan. We matched BNT162b2-vaccinated and -unvaccinated individuals in a 1:1 ratio on the date of vaccination of the vaccinated individual. We evaluated the effectiveness of the vaccine against infection, symptomatic infection, and coronavirus disease (COVID-19)-related hospitalization by comparing the vaccinated and unvaccinated groups. We estimated the risk ratio and risk difference using the Kaplan–Meier method with inverse probability weighting. The vaccine effectiveness was calculated as (1 − risk ratio) × 100%.Results: The study included 203,574 matched pairs aged ≥65 years. At 7 days after the second dose, the vaccine effectiveness of BNT162b2 against infection, symptomatic infection, and hospitalization was 78.1% (95% confidence interval CI, 65.2–87.8%), 79.1% (95% CI, 64.6–88.9%), and 93.5% (95% CI, 83.7–100%), respectively.Conclusion: BNT162b2 was highly effective against infection, symptomatic infection, and hospitalization in Japan’s older adult population aged ≥65 years during the Delta-predominant period.