Most studies of COVID-19 vaccine hesitancy among health care workers (HCWs) have been descriptive, few have tested models to predict hesitancy, and none have examined the possible relationship between HCWs’ distress and vaccine hesitancy. This study examined predictors of COVID-19 vaccine hesitancy, including HCWs’ distress after taking into account HCW sex, doctoral-level status, race, age, and exposure to COVID-19. Further, it examined specific reasons HCWs endorsed for their hesitancy. 266 HCWs in the United States (U.S.). completed an online survey administered in January 2021, following the availability of the vaccine for HCWs in the U.S. The survey assessed demographics, depression, anxiety, COVID-19 vaccine hesitancy, and reasons for hesitancy. A comprehensive linear regression model explained 72.2% of the variance in COVID-19 vaccine hesitancy. HCWs were more hesitant if they did not know someone personally who had tested positive. Distress had no effect. The reasons most predicting vaccine hesitancy included safety, potential side effects, believing the risks from COVID-19 were lower than from the vaccine, not feeling at risk for getting COVID-19, and current pregnancy. Rather than rely on providing information about the COVID-19 vaccines to HCWs, strategies that address their concerns are required to promote vaccine acceptance. Contemporary issues of political polarization, misinformation and mistrust are likely to contribute to the concerns HCWs have about the COVID-19 vaccines.