Objective To explore the effects of endoscopic reprocessing on disinfection and its influential factors under the coronavirus disease 2019 (COVID-19) pandemic. Methods A total of 450 endoscopes cleaned and disinfected according to Technical Specifications for Cleaning and Disinfection of Endoscopes from November 2019 to January 2020, and 450 endoscopes cleaned and disinfected according to The recommended procedure for cleaning and disinfection of gastrointestinal endoscopes during COVID-19 epidemic by Chinese Society of Digestive Endoscopology from February to April 2020 in the Second Affiliated Hospital of Chongqing Medical University were enrolled in the control group and observation group respectively by random number method. Both the control group and the observation group contained 200 gastroscopes, 200 enteroscopes and 50 ultrasound endoscopes. ATP fluorescence detection method and pour plate technique were used to evaluate the disinfection effect of endoscopes. Single factor analysis and multiple logistic regression were used to analyze the risk factors for unqualified sterilization after endoscopic reprocessing. Results The disinfection pass rates of gastroscopes, enteroscopes and ultrasound endoscopes in the observation group were not significantly different compared with those of the control group (P>0.05). The sterilization pass rates and ATP test pass rates of gastroscopes, enteroscopes and ultrasound endoscopes in the observation group were significantly higher than those in the control group (all P<0.05). Multivariate logistic regression analysis showed that non-strict implementation of endoscopic reprocessing (OR=7.96, 95%CI: 4.55-22.84, P＜0.001), non-standard operation (OR=2.26, 95%CI: 1.24-5.63, P＜0.001), insufficient concentration of disinfectant (OR=5.43, 95%CI: 2.52-9.02, P＜0.001), insufficient concentration ratio of multi-enzyme solution (OR=4.38, 95%CI: 1.95-8.61, P＜0.001), non-timely cleaning (OR=2.86, 95%CI: 1.33-6.42, P＜0.001), incomplete cleaning (OR=3.75, 95%CI: 1.61-7.49, P＜0.001) and improper endoscopic preservation (OR=2.12, 95%CI: 1.36-4.12, P＜0.001) were independent risk factors for unqualified sterilization after endoscopic reprocessing. Conclusion In COVID-19 pandemic, endoscope reprocessing can significantly improve the disinfection effect of endoscopes, worthy of further clinical promotion. The failure to strictly implement the reprocessing procedure is an important factor that may lead to unqualified sterilization.