Background: since COVID-19 emergence in December 2019, health systems in collaboration with scientists all over the world struggled to face this pandemic. Population acceptance of vaccination is a very important factor necessary to achieve herd immunity. This study aimed to assess the prevalence of vaccine acceptance and its predictors among the Egyptian population. Methods: An online cross-sectional study was conducted on a total sample of 846 individuals selected by using the non-probability snowball sampling technique during August and September 2021. Data was collected by An Arabic questionnaire which included data on the socio-economic characters of the participants, health-related variables, and the outcome variable (participants' vaccine acceptance). The odds ratio and 95% confidence interval were used to identify the association between vaccine acceptance and socio-demographic and health-related variables. Results: Of 846 participants, 467 accept vaccination representing 55.2% of the total sample. Vaccine acceptance was associated with a higher age group (>50 years), male gender, urban residents, educated, married, high-income individuals, and healthcare workers. Also, vaccine acceptance was associated with a history of chronic disease, fair/poor self-rated health status, negative history of COVID-19 infection, and a high perception of the infection risk. About 83.4% of vaccine refusals believed that the vaccine is not safe, while 50.7% believed it is ineffective. Conclusion: Socio-demographic and some health-related characters are significant predicators of vaccine acceptance among the population. These variables must be taken into consideration in interventions aimed to increase the population vaccination rate.