Abstract Background Surgical site infections represent a prevalent postoperative complication, significantly impacting patient safety and increasing the burden on healthcare resources. As a key measure for preventing these infections, preoperative skin antisepsis plays a crucial role. However, current meta-analyses and international guidelines have yet to reach a unified agreement on the optimal type and concentration of antiseptic preparation. This study aims to compare the efficacy of chlorhexidine in alcohol and aqueous povidone-iodine in preventing surgical site infections through systematic review and meta-analysis. Methods A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) comparing the preoperative skin antisepsis effects of chlorhexidine in alcohol and aqueous povidone-iodine up to May 31, 2025. The primary outcome was the incidence of surgical site infections, while secondary outcomes included adverse events. Subgroup analyses were conducted according to chlorhexidine concentration, wound classification, and surgical category. The meta-analysis was conducted using R software, with a statistical threshold of P < 0.05 for significance. To evaluate the robustness of the findings, sensitivity analysis and trial sequential analysis (TSA) were conducted. Results The meta-analysis included 17 RCTs involving 13,737 patients. The results revealed that chlorhexidine in alcohol was significantly more effective than aqueous povidone-iodine in preventing surgical site infections (RR = 0.84, 95% CI: 0.73–0.95, P < 0.01; I² = 14%). Subgroup analyses further demonstrated that 2.0%-2.5% chlorhexidine in alcohol (RR = 0.83, 95% CI: 0.71–0.97, P = 0.02; I² = 32%) was associated with a lower SSI risk than aqueous povidone-iodine. Furthermore, in non-clean surgery (RR = 0.85, 95% CI: 0.75–0.97, P = 0.01; I² = 0%) and general surgery (RR = 0.70, 95% CI: 0.53–0.92, P = 0.01; I² = 65%), chlorhexidine in alcohol was associated with a significantly lower SSI risk. Sensitivity analyses showed consistent results across individual studies, and TSA suggested that the accumulated evidence has reached the required information size. However, the interpretation of subgroup findings should consider residual heterogeneity in some subgroups and the risk of bias of included trials. Conclusion Compared with aqueous povidone-iodine, chlorhexidine in alcohol was associated with a lower risk of surgical site infections, particularly in non-clean surgery and at chlorhexidine concentrations of 2.0%-2.5%.
Zhu et al. (Mon,) studied this question.
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