Comparative Effectiveness of Chlorhexidine-Alcohol and Povidone-Iodine in Preventing Surgical Site Infections: A Systematic Review and Meta-Analysis

Surgical site infections (SSIs) remain a leading cause of postoperative morbidity. While both chlorhexidine-alcohol (CHG-A) and povidone-iodine (PVI) are standard preoperative skin antiseptics, their comparative efficacy, particularly in clean-contaminated surgeries, where the benefit of CHG-A’s persistent activity is most theorized, remains a subject of ongoing clinical debate. This meta-analysis aimed to evaluate whether CHG-A is superior to PVI in preventing SSIs in adult patients undergoing elective surgery, with a specific focus on clean-contaminated procedures. The primary outcome was overall SSI incidence within 30 days; secondary outcomes included deep incisional SSI, superficial incisional SSI, and adverse skin reactions. We conducted a systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Web of Science, EMBASE, and the Cochrane Library were searched from inception to January 31, 2026, without language restrictions. We included randomized controlled trials (RCTs) comparing CHG-A with PVI for preoperative skin preparation in adults undergoing elective surgery and reporting 30-day SSI rates using standardized definitions. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. A random-effects model (DerSimonian-Laird method) was used for the meta-analysis, with heterogeneity quantified using the I² statistic. A prespecified subgroup analysis was conducted for clean-contaminated surgeries, and a leave-one-out sensitivity analysis was performed. Nine RCTs (n = 8,000 patients) were included. For overall SSI, no significant difference was found between CHG-A and PVI (risk ratio (RR) = 0.84, 95% CI: 0.66-1.07; I² = 48%). In a prespecified subgroup of five studies on clean-contaminated surgeries, the RR was 0.77 (95% CI: 0.58-1.03). Deep incisional SSI rates were lower with CHG-A, although not statistically significant (RR = 0.75, 95% CI: 0.53-1.07). Heterogeneity stemmed from variability in surgery types and antiseptic formulations. Sensitivity analysis indicated robustness, with the most substantial effect change occurring upon omission of a large cardiac surgery trial. This meta-analysis did not find conclusive evidence that CHG-A is superior to PVI for preventing overall SSI across all surgery types. A nonsignificant trend favoring CHG-A was observed in clean-contaminated procedures and for deep SSIs, suggesting a context-dependent effect that warrants targeted investigation. Clinical choice may consider the specific surgical context, cost, and institutional protocols.