This study evaluates the effectiveness of the BNT162b2 mRNA vaccine against Covid-19 in a nationwide mass vaccination setting in Israel. The study matched 596,618 newly vaccinated individuals to unvaccinated controls in a 1:1 ratio based on demographic and clinical characteristics. The outcomes assessed included documented infection, symptomatic Covid-19, hospitalization, severe illness, and death. The estimated vaccine effectiveness was 46% for documented infection and 57% for symptomatic Covid-19 within 14 to 20 days after the first dose, and 92% for documented infection and 94% for symptomatic Covid-19 after 7 or more days after the second dose. The effectiveness increased over time, with higher rates observed for hospitalization, severe illness, and death. The study found consistent effectiveness across age groups but slightly lower effectiveness in individuals with multiple coexisting conditions. The results suggest that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19-related outcomes, supporting its use in mass vaccination campaigns.This study evaluates the effectiveness of the BNT162b2 mRNA vaccine against Covid-19 in a nationwide mass vaccination setting in Israel. The study matched 596,618 newly vaccinated individuals to unvaccinated controls in a 1:1 ratio based on demographic and clinical characteristics. The outcomes assessed included documented infection, symptomatic Covid-19, hospitalization, severe illness, and death. The estimated vaccine effectiveness was 46% for documented infection and 57% for symptomatic Covid-19 within 14 to 20 days after the first dose, and 92% for documented infection and 94% for symptomatic Covid-19 after 7 or more days after the second dose. The effectiveness increased over time, with higher rates observed for hospitalization, severe illness, and death. The study found consistent effectiveness across age groups but slightly lower effectiveness in individuals with multiple coexisting conditions. The results suggest that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19-related outcomes, supporting its use in mass vaccination campaigns.