Abstract: OBJECTIVE To systematically explore the development pathway of a long-term mechanism for perioperative infection prevention and control based on the practical experience of the "Perioperative Infection Control Initiative", thereby summarizing generalizable management insights. METHODS Based on a before-and-after comparative design, we enrolled a total of 9 532 elective surgery patients at Nanjing LiShui People's Hospital from Jul. 2024 to Jun. 2025. The patients were divided into a control group (from Jul. 2024 to Dec. 2024, n=4 728) and an intervention group (from Jan. 2025 to Jun. 2025, n=4 804). The intervention group received systematic, full-process comprehensive interventions based on the Donabedian three-dimensional quality model, covering standardized preoperative preparation, intraoperative aseptic and temperature management, postoperative catheter care, and enhanced recovery measures. A multi-departmental collaboration and an informatized monitoring mechanism were also established. RESULTS In terms of process indicators, the intervention group showed significant improvements: the intraoperative active warming rate increased from 93.55% to 99.21% (P<0.001), the effective execution rate of respiratory function training rose from 23.82% to 53.46% (P<0.001), and the incidence of intraoperative hypothermia decreased from 0.08% to 0.04%, though the difference was not statistically significant (P=0.410). Compared with the control group, the intervention group demonstrated significant improvements in infection prevention and control indicators: preoperative skin cleaning compliance increased from 45.60% to 86.74%, and correct hair removal practices improved from 43.78% to 73.42% (both P<0.001). The overall surgical site infection rate decreased from 1.04% to 0.37% (P<0.001), and the postoperative pneumonia rate dropped from 1.18% to 0.65% (P=0.006). The standardized use of antimicrobial agents significantly improved, with preoperative administration within 0.5-1 hour reaching 99.24% (vs. 95.15% in the control group) and discontinuation within 24 hours for type I incisions reaching (98.30% vs. 94.46% in the control group) (both P<0.001). CONCLUSIONS The "Perioperative Infection Control Initiative," through the establishment of a systematic, standardized, and informatized perioperative infection prevention and control system, effectively reduces infection rates. Its experience provides a replicable and scalable management model for primary hospitals.