Global vaccine development efforts were accelerated in response to the damaging coronavirus disease 2019 (COVID-19) pandemic. A study evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing the incidence, hospitalizations, and deaths in the United States. Researchers developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were suggested to inject vaccination, whereas children under 18 years of age were not vaccinated. The study mentioned vaccine efficacy of 95% against disease following 2 doses administered 21 days apart, achieving 40% vaccine coverage of the overall population within 284 days. Variation was done in vaccine efficacy against infection and specified 10% pre-existing population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States. Vaccination was found to reduce the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%–5.0%) from 9.0% (95% CrI: 8.4%–9.4%) without vaccination, over 300 days. The highest relative reduction (54%–62%) was observed among individuals aged 65 and older. Vaccination noticeably reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%–66.7%), 65.6% (95% CrI: 62.2%–68.6%), and 69.3% (95% CrI: 65.5%–73.1%), respectively, across the same period. Results of the studies indicated that vaccination could have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, ongoing compliance with nonpharmaceutical interventions is essential to achieve this impact.