Objective To evaluate the effect of ECRS management model on the quality of prevention and control of hospital infection with multidrug-resistant organisms (MDROs). Methods The data related to the prevention and control of MDROs in the First Hospital of Nanchang in 2020 and 2021 were retrospectively collected. The hospital implemented routine MDRO infection prevention and control management in accordance with the Expert Consensus on the Prevention and Control of Multi-drug Resistant Bacteria Nosocomial Infection in 2020. On this basis, the hospital applied the four principles of the ECRS method to cancel, combine, rearrange and simplify the MDRO infection prevention and control management. The detection rate of MDROs on object surfaces, the incidence rate of hospital infection of MDROs, the compliance rate of hand hygiene, the implementation rate of contact isolation prevention and control measures, and the pass rate of MDRO infection prevention and control education assessment were analyzed and compared between the two years. Results The detection rate of MDROs on the surfaces in 2021 was lower than that in 2020 (9.39% vs. 31.63%). The hospital-acquired MDRO infection rate in 2021 was lower than that in 2020 (1.18% vs. 1.46%). The hand hygiene compliance rates of medical staff, workers and caregivers in 2021 were higher than those in 2020 (90.99% vs. 78.63%, 73.51% vs. 45.96%, 70.96% vs. 33.71%). The implementation rate of contact isolation prevention and control measures in 2021 was higher than that in 2020 (93.31% vs. 70.79%). The qualified rates of MDRO infection prevention and control education in medical personnel, workers and caregivers in 2021 were higher than those in 2020 (96.57% vs. 81.31%, 76.47% vs. 47.95%, 73.17% vs. 34.19%). All the differences above were statistically significant (P<0.05). Conclusion ECRS management mode can improve the execution and prevention level of MDRO hospital infection prevention and control, and reduce the incidence of MDRO hospital infection.