COVID-19 vaccine hesitancy is complex, with adults identifying various reasons for not getting vaccinated. Using data from the 2022 National Wellbeing Survey on 7612 U.S. adults aged 18–64, we identified how age, race/ethnicity, sex, marital status, education, income, employment status, partisanship, and metropolitan status are associated with COVID-19 vaccination status and three non-mutually exclusive types of vaccine hesitancy: 1) watchful, concerned about vaccine side effects and efficacy; 2) skeptics, distrust the vaccine, and 3) system distrusters, distrust government. A third of respondents overall (N = 2643) had not received at least one dose at the time of the survey. Among respondents who were not vaccinated, 67 % are classified as watchful, 53 % are skeptics, and 32 % are system distrusters. Results from logistic regression show that concerns about side effects and safety (watchfulness) appear to be major drivers for not getting vaccinated among females and among non-Hispanic Black and unmarried adults, whereas skepticism and distrust appear to be more important barriers among ages 25–44. All three types of hesitancy appear to be important contributors to lower vaccination uptake among low-income, low-education, and unemployed adults, and among individuals who voted for Donald Trump in the 2020 election (with skepticism and distrust being most endorsed by this group). Findings suggest that universal messaging and intervention strategies are unlikely to be effective in reducing vaccine hesitancy. Different messages, messengers, and tactics must be used with different groups.