Introduction: Vaccination against severe acute respiratory syndrome coronavirus (SARS-CoV-2) plays a major role in the global fight against the COVID-19 pandemic. However, the availability of and access to a safe COVID-19 vaccine alone may not be sufficient to curb the epidemic. Vaccine hesitancy—including delays and refusals—remains a major obstacle to achieving herd immunity. This study aimed to investigate public attitudes toward the COVID-19 vaccine. Methods: This descriptive and analytical study was conducted on 1,544 individuals over 30 years of age in South Khorasan Province, selected via convenience sampling through the SIB system. Data were collected using a questionnaire to measure attitudes, administered via telephone interviews. Statistical analyses included mean and standard deviation, frequency and percentage distributions, chi-square tests, independent samples t-tests, and logistic regression analyses, with a significance level set at P < 0.05. Results: The findings revealed variations in vaccination rates across demographic categories, including gender, education level, marital status, occupation, and place of residence. Key factors influencing hesitancy included doubts about the accuracy of vaccine-related information, strong fears of vaccination, and the belief that individuals who had not contracted COVID-19 were naturally resistant and did not require vaccination. Conclusion: Public attitudes, doubts, and concerns regarding the COVID-19 vaccine significantly impact vaccination coverage rates. Therefore, understanding the reasons behind vaccine hesitancy is essential for designing targeted interventions.