Abstract: OBJECTIVE To systematically evaluate the effects of single intervention of DRG payment reform and dual intervention of DRG combined with antimicrobial stewardship (AMS) on ICU antimicrobial agents management and health care-associated infections (HAIs) prevention and control so as to provide solid evidence for delicacy management of medical quality and optimization of interventional strategies. METHODS The data regarding the medical quality monitoring of the ICUs of Changshu Hospital Affiliated to Soochow University for 60 months were collected from Jan. 2021 to Dec. 2025 and were divided into the baseline period, DRG implementation period, dual intervention period and follow-up observation period. The differences in the indicators were observed and compared by means of Kruskal-WallisH test and Dunn test. After collinearity screening, the entropy weight-TOPSIS method was employed to construct a comprehensive score. A segmented interrupted time series model incorporating the pandemic covariate was established to quantify the immediate effects of the interventions and long-term variation trends. RESULTS There were significant differences in case-mix index (CMI), average consumable cost per case, antimicrobial use density (AUD), incidence of multidrug-resistant organisms (MDROs) infections, reporting rate of adverse drug reactions (ADR), and etiological submission rate among the four time periods (P＜0.05). The entropy weight method demonstrated that the reporting rate of ADR (27.69%) and the utilization rate of antibiotics (21.58%) were the core indicators for comprehensive evaluation. The TOPSIS comprehensive score exhibited a pattern of minor fluctuation during baseline period, followed by a decline during the DRG implementation period, a short-term rise during the dual intervention period, and a subsequent decline during the follow-up period. The interrupted time series analysis showed that the single DRG intervention had the impact on neither the immediate level nor the long-term trend of the comprehensive quality; the dual intervention could remarkably raise the comprehensive score (β=0.149,P=0.001), and the change of negative slope did not reached statistical significance after the intervention(β=-0.006,P=0.051). CONCLUSIONS The dual intervention of DRG combined with AMS can raise the short-term comprehensive effectiveness in antimicrobial management and HAIs prevention and control, but the effect lacks long-term sustainability. The single DRG reform has a limited effect on improving the comprehensive quality. It is necessary to establish a management system featuring collaborative intervention and long-term maintenance so as to promote continuous quality improvement.