Vaccine hesitancy remains a major barrier to achieving full population vaccination against highly infectious diseases, including COVID-19. This study analyzed 1941 anonymous questionnaires from Israeli healthcare workers and the general population regarding their willingness to accept a potential COVID-19 vaccine. Results showed that healthcare workers caring for COVID-19 patients and individuals considering themselves at higher risk were more likely to accept vaccination. In contrast, parents, nurses, and non-COVID-19 care workers expressed higher hesitancy. Vaccine hesitancy is influenced by personal risk perception, misinformation, and concerns about vaccine safety, particularly due to the rapid development of the vaccine. The study found that male sex and self-perceived disease risk were positive predictors of vaccine acceptance, while parenthood and being a nurse were negative predictors. Healthcare workers in internal medicine and COVID-19 departments showed higher acceptance rates. Unemployment during the pandemic was also a positive predictor of vaccine acceptance. However, concerns about vaccine safety, particularly its rapid development, were the main concerns among respondents. The study highlights the need for targeted educational campaigns to address vaccine hesitancy, especially among healthcare workers and the general population. These campaigns should focus on alleviating concerns about vaccine safety and efficacy, and promoting public understanding of the vaccine's benefits. The findings suggest that even among medically informed individuals, vaccine acceptance depends on personal risk-benefit perceptions. Effective communication and education are crucial to achieving high vaccination rates and controlling the pandemic.Vaccine hesitancy remains a major barrier to achieving full population vaccination against highly infectious diseases, including COVID-19. This study analyzed 1941 anonymous questionnaires from Israeli healthcare workers and the general population regarding their willingness to accept a potential COVID-19 vaccine. Results showed that healthcare workers caring for COVID-19 patients and individuals considering themselves at higher risk were more likely to accept vaccination. In contrast, parents, nurses, and non-COVID-19 care workers expressed higher hesitancy. Vaccine hesitancy is influenced by personal risk perception, misinformation, and concerns about vaccine safety, particularly due to the rapid development of the vaccine. The study found that male sex and self-perceived disease risk were positive predictors of vaccine acceptance, while parenthood and being a nurse were negative predictors. Healthcare workers in internal medicine and COVID-19 departments showed higher acceptance rates. Unemployment during the pandemic was also a positive predictor of vaccine acceptance. However, concerns about vaccine safety, particularly its rapid development, were the main concerns among respondents. The study highlights the need for targeted educational campaigns to address vaccine hesitancy, especially among healthcare workers and the general population. These campaigns should focus on alleviating concerns about vaccine safety and efficacy, and promoting public understanding of the vaccine's benefits. The findings suggest that even among medically informed individuals, vaccine acceptance depends on personal risk-benefit perceptions. Effective communication and education are crucial to achieving high vaccination rates and controlling the pandemic.