The epidemic of coronavirus disease 2019 (COVID-19) has seriously affected people's normal work, life, and medical treatment. Since Mar. 2022, there has been a pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant in Shanghai. In order to meet the needs of hospitalization for patients, and at the same time for better control of epidemic and nosocomial infections, a large hospital in Shanghai innovatively set up a centralized transition ward in the hospital, and established scientific rules of medical work, regulations for prevention of nosocomial infections and efficient norms for patient admission. During the operation of the ward, a total of 211 patients were treated and one of the patients was confirmed of COVID-19 recurrence. All work was carried out methodically, and neither hospitalized patients nor medical staff had nosocomial infection of COVID-19. The preparation, operation and management of the central transition ward in our hospital are summarized here to provide guidance and reference for general hospitals to carry out similar work under the epidemic.