Objective To investigate the effect of preserving prosthetic debridement for postoperative infection after initial total knee replacement. Methods Retrospective analysis of clinical data of 33 patients who were treated with retained prosthesis debridement for postoperative infection after initial total knee replacement in our department from January 2016 to June 2020, including 28 cases of infection within 3 months postoperatively and 5 cases within 4-6 months postoperatively. The patients' American Knee Society score KSS, visual analog score VAS, laboratory tests and postoperative infection recurrence and complications were recorded during the perioperative period and at the last follow-up. Results Bacterial culture was negative in 15 cases and positive in 18 cases. 33 patients were followed up for (42.6±9.2) months, 28 had successful surgeries (26 infections within 3 months and 2 infections within 4-6 months after surgery), 5 had failed surgeries, and 1 had a postoperative deep vein thrombosis. The postoperative KSS score increased significantly (P<0.05), VAS score decreased significantly (P<0.05), WBC, ESR and CRP decreased significantly (P<0.05) compared with those before surgery, and the last follow-up X-ray showed no loosening of the prosthesis. Conclusion Infections within 3 months after the initial replacement can achieve better early results with retained prosthesis debridement, and infections within 4-6 months after surgery have a higher failure rate.