By September 21, 2021, an estimated 182 million persons in the U.S. were fully vaccinated against COVID-19.* Clinical trials indicate that Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Johnson & Johnson; Ad.26.COV2.S) vaccines are effective and generally well tolerated (1-3). However, daily vaccination rates have declined approximately 78% since April 13, 2021|; vaccine safety concerns have contributed to vaccine hesitancy (4). A cohort study of 19,625 nursing home residents found that those who received an mRNA vaccine (Pfizer-BioNTech or Moderna) had lower all-cause Mortality than did unvaccinated residents (5), but no studies comparing Mortality rates within the general population of vaccinated and unvaccinated persons have been conducted. To assess Mortality not associated with COVID-19 (non-COVID-19 Mortality) after COVID-19 vaccination in a general population setting, a cohort study was conducted during December 2020-July 2021 among approximately 11 million persons enrolled in seven Vaccine Safety Datalink (VSD) sites.| After standardizing Mortality rates by age and sex, this study found that COVID-19 vaccine recipients had lower non-COVID-19 Mortality than did unvaccinated persons. After adjusting for demographic characteristics and VSD site, this study found that adjusted relative risk (aRR) of non-COVID-19 Mortality for the Pfizer-BioNTech vaccine was 0.41 (95% confidence interval [CI] = 0.38-0.44) after dose 1 and 0.34 (95% CI = 0.33-0.36) after dose 2. The aRRs of non-COVID-19 Mortality for the Moderna vaccine were 0.34 (95% CI = 0.32-0.37) after dose 1 and 0.31 (95% CI = 0.30-0.33) after dose 2. The aRR after receipt of the Janssen vaccine was 0.54 (95% CI = 0.49-0.59). There is no increased risk for Mortality among COVID-19 vaccine recipients. This finding reinforces the safety profile of currently approved COVID-19 vaccines in the U.S.