The emergence of new coronavirus variants and evidence of waning immunity offered by COVID-19 vaccines draw attention to the need for regular vaccination. Vaccine hesitancy is one of the top ten threats to global health. There is a dearth of knowledge on people’s hesitancy to take regular COVID-19 vaccines. This study aimed to investigate the prevalence and determinants of hesitancy for regular COVID-19 vaccination. A population-based, random telephone survey was performed in Hong Kong in April 2022 (n = 1213). The age-standardized hesitancy rate for regular COVID-19 vaccines among Hong Kong adults was 39.4% (95% CI = 35.3–44.1%), exhibiting a sloping S-shape with age. Regression analyses revealed that females, young adults, self-perceived fair/bad health, low COVID-19 vaccine uptake, and believing there are better ways for prevention of infection were positive determinants of hesitancy for regular vaccination. Vaccine confidence, perceived severity and availability, trust in manufacturers and government, and civic duty inclination were negative determinants. Tailored vaccine promotions are needed for females, young adults, and people perceiving poor health and receiving fewer doses. Information on infection severity, vaccine availability, and trust in suppliers, products, and governments are key attitude-change facilitators to decrease hesitancy for regular COVID-19 vaccination and cope with future pandemics.