When a clustered coronavirus disease 2019 epidemic occurs, how to prevent and control hospital infection is a challenge faced by each medical institution. Under the normalization situation, building an effective prevention and control system is the premise and foundation for medical institutions to effectively prevent and control infection when dealing with clustered epidemics. According to the principles of control theory, medical institutions should quickly switch to an emergency state, and effectively deal with the external and internal infection risks brought by clustered epidemics by strengthening source control measures, engineering control measures, management control measures and personal protection measures. This article summarizes the experience of handling clustered outbreaks in medical institutions in the prevention and control of coronavirus disease 2019, and aims to provide a reference for medical institutions to take effective prevention and control measures when dealing with clustered outbreaks.