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The COVID-19 pandemic underscores the significance of vaccine hesitancy in shaping vaccination outcomes. Understanding the factors underpinning COVID-19 vaccination hesitancy is crucial for tailoring effective vaccination strategies. This cross-sectional study, conducted in three communities across the United States and Lebanon, employed surveys to assess respondents' knowledge, attitudes, and perceptions regarding COVID-19 infection and vaccination. Among the 7196 participants, comprising 6775 from the US and 422 from Lebanon, vaccine hesitancy rates were comparable at 12.2% and 12.8%, respectively. Notably, a substantial proportion of respondents harbored misconceptions, such as attributing the potential to alter DNA (86.4%) or track individuals (92.8%) to COVID-19 vaccines and believing in the virus's artificial origins (81%). US participants had more misconceptions about the COVID-19 vaccine, such as altering DNA or causing infertility. Lebanese participants were more likely to question the origins of the virus and the speed of vaccine development. Additionally, US respondents were less worried about infection, while Lebanese respondents were more indecisive but less likely to outright reject the vaccine. Primary determinants of hesitancy included perceptions that the vaccine poses a greater risk than the infection itself (aOR = 8.7 and 9.4, respectively) and negative recommendations from healthcare providers (aOR = 6.5 and 5.4, respectively). Conversely, positive endorsements from healthcare providers were associated with reduced hesitancy (aOR = 0.02 and 0.4, respectively). Targeting healthcare providers to dispel misinformation and elucidate COVID-19 vaccine risks holds promise for enhancing vaccination uptake. [ABSTRACT FROM AUTHOR]