This study quantifies the global impact of the first year of COVID-19 vaccination programs, using a mathematical model to estimate the number of lives saved. The model was fit to reported COVID-19 mortality and all-cause excess mortality in 185 countries and territories. Based on official reported COVID-19 deaths, the study estimated that vaccinations prevented 14.4 million deaths (95% credible interval [CrI] 13.7–15.9) from COVID-19 between December 8, 2020, and December 8, 2021. When using excess mortality as an estimate of the true pandemic extent, the number of averted deaths increased to 19.8 million (95% CrI 19.1–20.4), representing a 63% reduction in total deaths during the first year of vaccination. In COVAX Advance Market Commitment countries, 41% (7.4 million [95% CrI 6.8–7.7] of 17.9 million deaths) of excess mortality was averted. In low-income countries, an additional 45% (95% CrI 42–49) of deaths could have been averted if the 20% vaccination coverage target set by COVAX had been met, and an additional 111% (105–118) of deaths could have been averted if the 40% target set by WHO had been met by the end of 2021. The study highlights the substantial impact of vaccination on the pandemic trajectory and underscores the importance of equitable vaccine distribution to maximize the lives saved.This study quantifies the global impact of the first year of COVID-19 vaccination programs, using a mathematical model to estimate the number of lives saved. The model was fit to reported COVID-19 mortality and all-cause excess mortality in 185 countries and territories. Based on official reported COVID-19 deaths, the study estimated that vaccinations prevented 14.4 million deaths (95% credible interval [CrI] 13.7–15.9) from COVID-19 between December 8, 2020, and December 8, 2021. When using excess mortality as an estimate of the true pandemic extent, the number of averted deaths increased to 19.8 million (95% CrI 19.1–20.4), representing a 63% reduction in total deaths during the first year of vaccination. In COVAX Advance Market Commitment countries, 41% (7.4 million [95% CrI 6.8–7.7] of 17.9 million deaths) of excess mortality was averted. In low-income countries, an additional 45% (95% CrI 42–49) of deaths could have been averted if the 20% vaccination coverage target set by COVAX had been met, and an additional 111% (105–118) of deaths could have been averted if the 40% target set by WHO had been met by the end of 2021. The study highlights the substantial impact of vaccination on the pandemic trajectory and underscores the importance of equitable vaccine distribution to maximize the lives saved.