Background The COVID-19 pandemic is expected to continue to inflect immense burdens of morbidity and mortality, not to mention the sever disruption of societies and economies worldwide. One of the major challenges to managing COVID-19 pandemic is the negative attitudes towards vaccines and the uncertainty or unwillingness to receive vaccinations. We evaluated the predictors and factors behind the negative attitudes towards COVID-19 vaccines in 3 countries in the Middle East. Methods A cross-sectional, self-administered survey was conducted between the 1st and the 25th of December, 2020. Representative sample of 8619 adults residing in Jordan, West Bank, and Syria, completed the survey via the Web or via telephone interview. The survey intended to assess intent to be vaccinated against COVID-19 and to identify predictors of and reasons among participants unwilling/hesitant to get vaccinated. Results The total of the 8619 participants included in this study were the ones who answered the question on the intent to be vaccinated. Overall, 32.2% of participants (n = 2772) intended to be vaccinated, 41.6% (n = 3589) didn’t intend to get vaccinated, and 26.2% (n = 2258) were not sure. The main factors associated with the willingness to take the vaccine (yes responses) included females, 18–35 years old, Syrians and Jordanians, a large family size, and having received a flu vaccine last year. Reasons for vaccine hesitancy included the lack of rigorous evaluation of the vaccine by the FDA and the possible long-term health risks associated with the vaccines (the wait-and-see approach). Conclusion This survey, conducted in December when the number of cases and deaths per day due to COVID-19 were at or near peak levels of the initial surge in the three regions under investigation. The survey revealed that most of survey’s participants (67.8%) were unwilling/hesitant to get vaccinated against COVID-19 with the lack of trust in the approval process of the vaccine being the main concern; the two main characteristics of those participants were more than 35 years old and participants holding a Bachelor’s degree or higher. Targeted and multi-pronged efforts will be needed to increase acceptance of COVID-19 vaccine in Jordan, West Bank and Syria.

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