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Objectives. To characterize COVID-19 vaccine uptake and hesitancy among US nurses. Methods. We surveyed nurses in 3 national cohorts during spring 2021. Participants who indicated that they did not plan to receive or were unsure whether they planned to receive the vaccine were considered vaccine hesitant. Results. Among 32 426 female current and former nurses, 93% had been or planned to be vaccinated. After adjustment for age, race/ethnicity, and occupational variables, vaccine hesitancy was associated with lower education, living in the South, and working in a group care or home health setting. Those who experienced COVID-19 deaths and those reporting personal or household vulnerability to COVID-19 were less likely to be hesitant. Having contracted COVID-19 doubled the risk of vaccine hesitancy (95% confidence interval [CI] = 1.85, 2.53). Reasons for hesitancy that were common among nurses who did not plan to receive the vaccine were religion/ethics, belief that the vaccine was ineffective, and lack of concern about COVID-19; those who were unsure often cited concerns regarding side effects or medical reasons or reported that they had had COVID-19. Conclusions. Vaccine hesitancy was unusual and stemmed from specific concerns. Public Health Implications. Targeted messaging and outreach might reduce vaccine hesitancy. ( Am J Public Health . 2022;112(11):1620-1629. https://doi.org/10.2105/AJPH.2022.307050).