Florida adults who received the BNT162b2 COVID-19 vaccine in the initial series had higher risk of 12-month all-cause, cardiovascular, COVID-19, and non-COVID-19 mortality compared to matched mRNA-1273 recipients, with differences in cardiovascular and COVID-19 mortality primarily driven by adults 60 and older. These findings suggest that COVID-19- and non-COVID-19-related health outcomes should be considered when evaluating vaccines targeting SARS-CoV-2.