BackgroundNovel coronavirus disease 2019 (COVID-19) vaccine hesitancy is a barrier to achieving herd immunity, and thus, a prominent public health concern. This study aimed to identify the determinants of COVID-19 vaccine hesitancy based on the World Health Organization’s ‘3Cs’ model (i.e., confidence, complacency, and convenience) in the United States (U.S.) and Canada.MethodsData from 7678 adults ages 18 or older were collected from the four most populous U.S. States, specifically New York, California, Florida, and Texas, and from English-speaking Canada at three timepoints, in May and July 2020, and March 2021 using a web-based survey (www.covid19-database.com). Sociodemographic information was collected, and comprehensive psychological assessments were administered. Univariate analyses were performed to identify the individual determinants of vaccine hesitancy, which were categorized as: 1) vaccine confidence, 2) vaccine complacency, 3) sociodemographic, and 4) other psychological factors. A series of models were computed using these categorizations.ResultsMistrust of vaccine benefit (β(SE) = 0.67(0.01), p<0.001, partial η2 = 0.26) and lower perceived seriousness of COVID-19 (β(SE) = 0.68(0.02), p<0.001, partial η2 = 0.12) were the principal determinants of vaccine hesitancy. Right-wing political affiliation (β(SE) = 0.32(0.02), p<0.001, partial η2 = 0.03), higher risk propensity (β(SE) = 0.24(0.02), p<0.001, partial η2 = 0.03), and less negative mental health effects of the COVID-19 pandemic (β(SE) = 0.20(0.01), p<0.001, partial η2 = 0.03) were the main sociodemographic and psychological determinants. Other sociodemographic determinants included younger age, women, race, and employment status. Lack of vaccine confidence and complacency explained 38% and 21% of the variance in vaccine hesitancy, respectively; whereas, sociodemographic and psychological determinants explained 13% and 11% of the variance in vaccine hesitancy, respectively.DiscussionTargeted and tailored public health interventions that enhance the public’s confidence in vaccines and emphasize the risk and seriousness of COVID-19 may address COVID-19 vaccine hesitancy. Efforts directed toward specific marginalized and underserved groups may be required to promote vaccine confidence.