OBJECTIVE: The purpose of this study was to determine whether intrapartum chlorhexidine vaginal irrigations prevent peripartal infection in nulliparous women at ≥32 weeks of gestation. STUDY DESIGN: This was a double-blinded, placebo-controlled randomized clinical trial. Vaginal irrigations were performed with 200 mL of 0.2% chlorhexidine solution or sterile saline solution placebo every 6 hours during labor. The primary study outcome was clinically diagnosed maternal peripartal infection: chorioamnionitis or endometritis. Analysis was by intent to treat. RESULTS: One thousand forty-one women were assigned randomly to one of two groups (chlorhexidine therapy, 525 women; placebo, 516 women). The two groups were balanced for risk factors for infection. Rates of peripartal infection were 19.3% in the chlorhexidine group and 17.3% in the placebo group (relative risk 1.1; 95% Cl, 0.9-1.4). Major and minor neonatal morbidities were similar between the groups. No major and one minor adverse reaction was attributed to chlorhexidine irrigation. CONCLUSION: Under the conditions of this trial, chlorhexidine vaginal irrigation lacked efficacy in the prevention of clinically diagnosed maternal and neonatal infectious morbidity.