There is strong evidence regarding the efficacy and effectiveness of the BNT162b2 vaccine in preventing symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is a relative paucity of data regarding its effectiveness in the prevention of asymptomatic infection.In this real-world observational study, we identified a subpopulation of individuals in a large health maintenance organization who were repeatedly tested for SARS-CoV-2 infection by polymerase chain reaction (PCR). We included these individuals in the study cohort and compared those who were vaccinated with BNT162b2 mRNA vaccine to unvaccinated individuals. A positive SARS-CoV-2 PCR test result was used as the outcome. The follow-up period was from January 1, 2021, until February 11, 2021.A total of 6286 individuals were included in the cohort. Seven days after the second vaccine dose, a rate of 6 positive PCR tests per 10 000 person-days was recorded, compared with a rate of 53 positive tests per 10 000 person-days for the unvaccinated group. The estimated vaccine effectiveness against infection with SARS-CoV-2 virus after 2 vaccine doses was 89% (95% CI, 82%-94%). The estimated effectiveness 2 weeks after the first vaccine dose was 61% (95% CI, 49%-71%).In this study, vaccination with BNT162b2 reduced infection rates among individuals who underwent screening by frequent SARS-CoV-2 PCR testing. Using a cohort of frequently tested individuals reduced the indication bias for the PCR testing, which enabled estimation of infection rates.