Background: Vaccine hesitancy can limit the benefits of available vaccines in halting the spread of COVID-19 pandemic. Previously published studies paid little attention to Arab countries, which has a population of over 440 million. In this study, we present the results of the first large-scale multinational study that measures vaccine hesitancy among Arab-speaking subjects.Methods: An online survey in Arabic was conducted from 14-Jan-2021 to 29-Jan-2021. It consisted of 17 questions capturing demographic data, acceptance of COVID-19 vaccine, attitudes towards the need for COVID-19 vaccination and associated health policies, and reasons for vaccination hesitancy. R software- v.4.0.2 was used for data analysis and visualization.Results: The survey recruited 36,220 eligible participants (61.1% males, 38.9% females, mean age 32.6±10.8 years) from all the 23 Arab countries and territories (83.4%) and 122 other countries (16.6%). Our analysis shows a significant rate of vaccine hesitancy among Arabs in and outside the Arab region (83% and 81%, respectively). The most cited reasons for hesitancy are concerns about side effects and distrust in healthcare policies, vaccine expedited production, published studies and vaccine producing companies. We also found that female participants, participants 30-59 year-old, those with no chronic diseases, those with lower-level of academic education, and those who do not know the type of vaccine authorized in their countries are more hesitant to receive COVID-19 vaccination. On the other hand, participants who regularly receive the influenza vaccine, health care workers, and those from countries with higher rates of COVID-19 infections showed more vaccination willingness. Interactive representation of our results is posted on our project website at https://mainapp.shinyapps.io/CVHAA.Conclusion: Our results show higher vaccine hesitancy and refusal among Arab subjects, related mainly to distrust and concerns about side effects. Health authorities and Arab scientific community have to transparently address these concerns to improve vaccine acceptance.Funding: This study received no funding.