(1)Background and Objectives:There were two distinct coronavirus disease 2019 (COVID-19) outbreaks in 2020 and 2022 at a long-term mental health facility (LTMHF) in Gyeonggi Province, Korea. We aimed to compare the two outbreaks and identify differences in epidemiological and clinical outcomes due to changes in epidemic timing and management methods. (2)Materials and Methods: The structural, operational, and case-specific LTMHF data of COVID-19-confirmed patients during these outbreaks in 2020 and 2022 were retrospectively analyzed. (3)Results: Forty individuals (37 residents) in 2020 and thirty-nine (32 residents) in 2022 were confirmed to have COVID-19, and ten were infected twice. Facility isolation was implemented as an infection control measure, and one COVID-19-related death occurred in 2020. All residents and staff were vaccinated at least twice in 2022; moreover, in 2022, 38 patients (97.4%) received a third vaccination less than months before infection. The average Ct value of the cases in 2022 was significantly higher than that in 2020; however, vaccine-breakthrough (V-BT) and reinfection after vaccination rates were similar. (4)Conclusions: COVID-19 vaccination could help lower the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was inversely correlated with Ct values, and ventilation system improvements in health facilities might reduce transmissibility.