Purpose: Around 70% of the Iranian population had received two doses of coronavirus disease 2019 (COVID-19) vaccines by the end of 2021. In this study, we evaluated the reasons for vaccination refusal among people in Ahvaz, Iran. Materials and Methods: In this cross-sectional study, 800 participants (400 vaccinated and 400 unvaccinated) were recruited. A demographic questionnaire was completed through interviews. The unvaccinated participants were asked about the reasons for their refusal. The Shapiro-Wilk test, independent t-test, chi-square test, and logistic regression were used for analyzing data. Results: Older people were 1.018 times more likely to refrain from vaccination (95% confidence interval [CI], 1.001–1.039; p=043). People who were manual workers as well as those who were unemployed/housewives were 0.288 and 0.423 times less likely to receive vaccination, respectively. Those with high school education and married women were 0.319 and 0.280 times less likely to receive vaccination, respectively (95% CI, 198–0.515; p<0.001; 95% CI, 0.186–0.422; p<0.001). Participants who had hypertension or suffered from neurological disorders were more likely to receive the vaccination. Finally, people affected with severe COVID-19 infection were 3.157 times more likely to get vaccinated (95% CI, 1.672–5.961; p<0.001). Conclusion The results of this study showed that lower level of education and older age were contributed to reluctance for vaccination, while having chronic diseases or being already infected with severe COVID-19 infection were associated with more acceptance of vaccination.