To compare the effectiveness of vaginal antiseptic preparations administered before cesarean delivery in reducing postoperative infectious morbidity and to assess whether antiseptic type and concentration influence outcomes.

PubMed/MEDLINE, Embase, Web of Science, Scopus, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and gray literature sources were searched from January 1, 1990 to January 24, 2025.

Randomized and quasi-randomized controlled trials of pregnant women undergoing cesarean delivery who received systemic antibiotic prophylaxis and were randomized to vaginal antiseptic preparation vs no vaginal preparation. Eligible studies reported at least one relevant outcome: endometritis, wound infection, wound complications, or postoperative fever.

Two reviewers independently screened, extracted data, and assessed risk of bias (Cochrane Risk of Bias 2.0) and research integrity using the Trustworthiness in RAndomized Controlled Trials checklist. Primary analyses pooled studies by antiseptic agent, with secondary analyses considering both agent and concentration. Both pairwise random-effects meta-analyses (direct comparisons) and network meta-analyses (indirect and mixed comparisons) were conducted within a Bayesian framework. Odds ratios were reported with 95% credible intervals and 95% prediction intervals. Network meta-analyses additionally estimated comparative effects, generated treatment rankings via the Surface Under the Cumulative Ranking Curve, and assessed global and local inconsistency. Prespecified subgroup analyses examined labor status, membrane rupture, and geographic setting; sensitivity analyses excluded nonliquid preparations and studies deemed untrustworthy.

Fifty trials (14,515 participants) evaluated povidone-iodine, chlorhexidine (0.05% to 5%), cetrimide, metronidazole, clindamycin, saline, water, and no vaginal preparation. Compared with patients who received chlorhexidine, those who did not receive vaginal preparation had significantly higher odds of endometritis (odds ratio, 3.65; 95% credible interval, 2.36–5.90), wound infection (odds ratio, 2.34; 95% credible interval, 1.66–3.36), wound complications (odds ratio, 2.28; 95% credible interval, 1.65–3.32), and postpartum fever (odds ratio, 3.60; 95% credible interval, 2.27–5.86) for unspecified concentration. In concentration-stratified analyses, chlorhexidine 0.2% achieved the highest Surface Under the Cumulative Ranking Curve for wound infection (0.995), and chlorhexidine of unspecified concentration ranked highest for fever (0.918). Clindamycin and cetrimide occasionally ranked highly but were supported by few, small trials. Subgroup and sensitivity analyses yielded consistent findings.

Vaginal antiseptic preparation before cesarean delivery reduces postoperative infectious morbidity. In contrast to earlier network meta-analyses, which identified povidone-iodine 1% as the top-ranked agent, our expanded analysis of 50 trials found chlorhexidine, particularly at low-range to mid-range concentrations, to be the most consistently effective across multiple outcomes, supported by the largest evidence base. Both antiseptic type and concentration influence effectiveness.