COVID-19 vaccination remains one of the most effective tools to reduce the risk of SARS-CoV-2 infection. Unfortunately, vaccine hesitancy has limited primary vaccination and booster uptake among the general population and HCWs. To gain a better understanding of factors associated with booster vaccine uptake, we analyzed COVID-19 vaccine booster rates among HCWs and identified risk factors associated with nonacceptance. Of the 62,387 HCWs included in our analysis, the overall booster uptake rate was 64.8%. Older age, Non-Hispanic White racial group, early initial vaccine uptake and longer duration of employment were associated with higher booster uptake. Significant differences were observed between different job categories. This persistence of vaccine hesitancy and disparities in COVID-19 booster uptake among HCWs, almost 2 years after the rollout of the COVID-19 vaccination, call for further efforts to increase vaccine confidence among HCWs and the general population in light of the continued need for further COVID-19 protection.