ImportanceSurgical infections are a major cause of perioperative morbidity and mortality, particularly in low-resource settings. Clean Cut, a 6-month quality improvement program developed by the global nonprofit organization Lifebox, has demonstrated improvements in postoperative infectious complications. However, the pilot program required intense external programmatic and resource support.ObjectiveTo examine the improvement in adherence to infection prevention and control standards and rates of postoperative infections in hospitals in the Clean Cut program after implementation strategies were updated and program execution was refined.Design, Setting, and ParticipantsThis cohort study evaluated and refined the Clean Cut implementation strategy to enhance scalability based on a qualitative study of its pilot phase, including formalizing programmatic and educational materials, building an automated data entry and analysis platform, and reorganizing hospital-based team composition. Clean Cut was introduced from January 1, 2019, to February 28, 2022, in 7 Ethiopian hospitals that had not previously participated in the program. Prospective data initiated on arrival in the operating room were collected, and patients were followed up through hospital discharge and with 30-day follow-up telephone calls.ExposureImplementation of the refined Clean Cut program.Main Outcomes and MeasuresThe primary outcome was surgical site infection (SSI); secondary outcomes were adherence to 6 infection prevention standards, mortality, hospital length of stay, and other infectious complications.ResultsA total of 3364 patients (mean [SD] age, 26.5 [38.0] years; 2196 [65.3%] female) from 7 Ethiopian hospitals were studied (1575 at baseline and 1789 after intervention). After controlling for confounders, the relative risk of SSIs was reduced by 34.0% after program implementation (relative risk, 0.66; 95% CI, 0.54-0.81; P < .001). Appropriate Surgical Safety Checklist use increased from 16.3% to 43.0% (P < .001), surgeon hand and patient skin antisepsis improved from 46.0% to 66.0% (P < .001), and timely antibiotic administration improved from 17.8% to 39.0% (P < .001). Surgical instrument (38.7% vs 10.2%), linen sterility (35.5% vs 12.8%), and gauze counting (89.2% vs 82.5%; P < .001 for all comparisons) also improved significantly.Conclusions and RelevanceA modified implementation strategy for the Clean Cut program focusing on reduced external resource and programmatic input from Lifebox, structured education and training materials, and wider hospital engagement resulted in outcomes that matched our pilot study, with improved adherence to recognized infection prevention standards resulting in a reduction in SSIs. The demonstration of scalability reinforces the value of this SSI prevention program.