We aimed to identify risk factors related to COVID-19 reinfection in Hong Kong. We performed a population-based retrospective cohort study and reviewed case-based data on COVID-19 infections reported to the Centre for Health Protection from 8 January 2020 to 29 January 2023. We analyzed the epidemiology of COVID-19 infections and performed a Cox regression analysis. In this period, 3.32% (103,065/3,106,579) of COVID-19 infections recorded were classified as reinfection. Compared with primarily infected cases, a higher proportion of re-infected cases had chronic diseases (33.54% vs. 27.27%) and were residents of residential care homes (RCH) (10.99% vs. 1.41%). The time interval between the two episodes ranged from 31 to 1,050 days (median 282 days). Cox regression analysis of Omicron cases with the adjustment of covariates showed that being female (Hazard Ratio [HR] 1.12, 95% CI 1.11-1.13), chronic diseases (HR 1.18, 95% CI 1.16-1.20) and RCH residents (HR 6.78, 95% CI 6.61-6.95) were associated with reinfection, while additional vaccination after primary infection was protective (HR 0.80, 95% CI 0.79-0.81). Further analytical studies on the risk factors and protectors of COVID-19 reinfection are needed to guide targeted interventions.