Background Mass vaccination is being used in response to coronavirus disease (COVID-19) epidemics, including those driven by emerging variants of concern. We evaluated the effectiveness of the inactivated whole-virus vaccine, CoronaVac, against symptomatic COVID-19 in the elderly population of Sao Paulo State, Brazil during widespread circulation of the P.1 variant. Methods We conducted a test-negative, case-control study of adults >=70 years of age from Sao Paulo State from January 17 to April 29, 2021, during which vaccination with a two-dose regimen of CoronaVac was implemented. We identified RT-PCR-confirmed COVID-19 cases as well as controls who had a symptomatic illness with a negative RT-PCR test from national surveillance and state vaccination databases. Controls were pair-matched to cases by age category, sex, self-report race, municipality, prior COVID-19 status, and date of RT-PCR testing. We estimated vaccine effectiveness, adjusted for age and comorbidities, using conditional logistic regression. Findings We selected 7,950 matched pairs with a mean age of 76 years from 26,433 COVID-19 cases and 17,622 test-negative controls. Adjusted vaccine effectiveness was 18.2% (95% CI, 0.0 to 33.2) and 41.6% (95% CI, 26.9 to 53.3) in the period 0-13 and ≥14 days, respectively, after the 2nd dose. Administration of a single vaccine dose was not associated with reduced odds of COVID-19. Vaccine effectiveness ≥14 days after the 2nd dose declined with increasing age and was 61.8% (95% CI 34.8 to 77.7), 48.9% (95% CI 23.3 to 66.0) and 28.0% (95% CI 0.6 to 47.9) among individuals 70-74, 75-79 and ≥80 years of age, respectively (pinteraction = 0.05). Interpretation CoronaVac was 42% effective in the real-world setting of extensive P.1 transmission, but significant protection was not observed until completion of the two-dose regimen and vaccine effectiveness declined with increasing age. These findings underscore the need to maintain non-pharmaceutical interventions when mass vaccination with CoronaVac is used as part of an epidemic response.