Objective To explore the effect of collaborative mode of adopting infection prevention and control (IPC) and antimicrobial stewardship (AMS) by medical institutions on reducing bacterial resistance. Methods Healthcare-associated infection (HAI) management and antimicrobial-related indicators, as well as multidrug-resis-tant organism (MDRO) detection rates of all hospitalized patients in a hospital from January 1, 2015 to December 31, 2022 were collected. The effectiveness of collaborative mode of IPC and AMS was evaluated. Results Compared with 2015-2016, the incidence of MDRO HAI in 2021-2022 decreased from 0.22% to 0.16% (P < 0.05), antimicrobial use density in hospitalized patients decreased from 48.48 to 42.17, antimicrobial use rate decreased from 49.45% to 45.21% (P < 0.05). The use rate of prophylactic antimicrobial agents in class Ⅰ incision surgery decreased from 48.62% to 33.13% (P < 0.05). Compared with 2017-2018, pathogen detection rate before antimicrobial therapy increased from 60.73% to 72.18% in 2021-2022 (P < 0.05). Compared with 2015-2016, except the detection rate of vancomycin-resistant Enterococcus faecalis slightly increased in 2021-2022, detection rates of other common MDRO decreased, especially methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, broad-spectrum β-lactamase-producing Klebsiella pneumoniae, broad-spectrum β-lactamase-producing Escherichia coli and fluoroquinolone-resistant Escherichia coli, differences were all statistically significant (all P < 0.05). Conclusion The collaborative mode of IPC and AMS can effectively promote the rational use of antimicrobial agents, decrease the occurrence and transmission of MDRO, and decrease bacterial resistance.