Background: Non-drug interventions are the most active and effective response strategies until the availability of 100% effective vaccines and antiviral drugs. As one of the important means of non-drug interventions, centralized medical observation plays a crucial role in the epidemic prevention and control. Methods: This retrospective study focused on the epidemic response in Putian city (Fujian, China) as the observation object, descriptive and qualitative analysis methods was discuss our practice and experience of the centralized medical observation during the epidemic response. Results: In September 2021, a total of 205 confirmed cases and 41 asymptomatic patients were reported in Putian city; a total of 11,201 contacts of all types were tracked and all were included in centralized medical observation; 110 centralized medical observation sites were put into use; 3,173 staff of various types were selected and dispatched to centralized medical observation sites to undertake the task of the epidemic prevention and control. Conclusion: Intensive medical observation assumes the tasks of isolation, health surveillance, nucleic acid testing, psychological assistance, infection prevention and control. It is an effective and practical strategy to deal with the epidemic of major infectious diseases caused by viruses transmitted via air or direct contact, such as the COVID-19.