Comparison of Metronidazole Gel and Povidone‑Iodine for Vaginal Preparation in Preventing Post‑Cesarean Infection‑Related Morbidity: A Three‑Group Randomized Controlled Trial

ABSTRACT Background and Aims Despite routine prophylactic antibiotics, post‐cesarean infectious morbidity remains a major challenge. Preoperative vaginal preparation can reduce vaginal microbial load, but direct comparisons are scarce. This study compared metronidazole gel versus povidone‐iodine for preventing post‐cesarean infection‑related complications. Methods This three‑arm randomized controlled trial was conducted at Fatemieh Hospital, Hamadan, Iran, from December 2025 to May 2026. A total of 201 women scheduled for elective cesarean delivery were randomized to metronidazole gel 0.75%, povidone‐iodine 10%, and control (n = 67 each). Primary outcomes were endometritis, postoperative fever, and surgical site infection (SSI). Secondary outcomes included need for additional antibiotics, length of hospital stay, readmission, and adverse events. Data were analyzed in Stata v.17 using ANOVA and chi‐square tests (p < 0.05). Results The composite infectious morbidity was significantly lower in the metronidazole group (6/67, 8.96%) compared to controls (21/67, 31.34%) (risk difference: 22.4%; 95% CI: 9.5%–35.3%; p = 0.002). Endometritis rates were 1/67 (1.49%), 3/67 (4.48%), and 8/67 (11.94%) in the metronidazole, povidone‐iodine, and control groups, respectively (p = 0.03). Fever rates were 2/67 (2.99%), 5/67 (7.46%), and 10/67 (14.93%) (p = 0.04). Need for additional antibiotics was lower in the metronidazole group (7/67, 10.45%) versus controls (18/67, 26.87%) (p = 0.04). Only the composite outcome remained significant after Bonferroni correction; individual outcomes did not. No significant differences were observed for SSI, readmission, or length of stay. Conclusions Metronidazole gel significantly reduced composite infectious morbidity compared with no vaginal preparation, an effect that remained significant after adjustment for multiple comparisons. While individual outcomes showed clinically meaningful reductions, statistical significance was not maintained after Bonferroni correction. Metronidazole gel may be a promising option for vaginal preparation, particularly in high‐risk settings. Trial Registration IRCT20251227068466N1.