Background: During the COVID-19 pandemic, hospitals not only deal with COVID-19 but also try to maintain their original functions. Nosocomial transmission of COVID-19 can disrupt such functions by infecting patients and healthcare workers. We attempted to determine a method to reduce nosocomial transmission of COVID-19 by analyzing exposure events and monitoring mask-wearing rates. Methods: From February 2020 to March 2021, we collected the results of the epidemiological investigation and surveillance data for COVID-19 exposure events at a tertiary teaching hospital in Korea with 1450 beds. We monitored the rates and appropriateness of wearing masks in all areas of the hospital from October 2020 to February 2021. Baseline epidemiologic data, means of exposure, rates of wearing masks, results of surveillance, and results of exposure events were analyzed. Results: There were 63 COVID-19 exposure events and 4,267 exposed individuals. Among them, 166 were isolated for 2 weeks. There was one secondary infection in which three healthcare workers were infected from a single index case. They worked in the same office room with the confirmed patient and showed multiple risk behaviors, including removing the mask during meals. There was no secondary infection among the exposed individuals who wore masks properly. Conclusion: To prevent nosocomial transmission and provide a safe environment for all individuals in the hospital, it is highly important to wear masks properly at all times.