OBJECTIVES: Vaccination and the emergence of the highly transmissible Omicron variant changed the fate of the COVID-19 pandemic. It is very challenging to estimate the number of lives saved by vaccination given the multiple doses of vaccination, the time-varying nature of transmissibility, the waning of immunity, and the presence of immune evasion. METHODS: We established a S-S-E-I-T-D-R model to simulate the number of lives saved by vaccination in six states in the United States (U.S.) from March 5, 2020, to March 23, 2023. The cumulative number of deaths were estimated under three vaccination scenarios based on two assumptions. Additionally, immune evasion by the Omicron and loss of protection afforded by vaccination or infection were considered. RESULTS: The number of deaths averted by COVID-19 vaccinations (including three doses) ranged from 0.154-0.295% of the total population across six states. The number of deaths averted by the third dose ranged from 0.008-0.017% of the total population. CONCLUSIONS: Our estimate of death averted by COVID-19 vaccination in the U.S. was largely in line with an official estimate (at a level of 0.15-0.20% of the total population). We found that the additional contribution of the third dose was small but significant.