Objective: To determine if cleansing the birth canal with an antiseptic at delivery reduces infections in mothers and babies postnatally. Design: Clinical trial; two months of no intervention were followed by three months of intervention and a final month of no intervention. Setting: Queen Elizabeth Central Hospital (tertiary care urban hospital), Blantyre, Malawi. Subjects: A total of 6965 women giving birth in a six month period and their 7160 babies. Intervention: Manual wipe of the maternal birth canal with a 0.25% chlorhexidine solution at every vaginal examination before delivery. Babies born during the intervention were also wiped with chlorhexidine. Main outcome measures: Effects of the intervention on neonatal and maternal morbidity and mortality. Results: 3635 women giving birth to 3743 babies were enrolled in the intervention phase and 3330 women giving birth to 3417 babies were enrolled in the non-intervention phase. There were no adverse reactions related to the intervention among the mothers or their children. Among infants born in the intervention phase, overall neonatal admissions were reduced (634/3743 (16.9%) v 661/3417 (19.3%), Pv 17.9 per 1000 live births, Pv 36.9 per 1000 live births, Pv 7.3 per 1000 live births, Pv 40.2 per 1000 deliveries, Pv 5.1 per 1000 deliveries, P=0.02) and duration of hospitalisation (Wilcoxon P=0.008). Conclusions: Cleansing the birth canal with chlorhexidine reduced early neonatal and maternal postpartum infectious problems. The safety, simplicity, and low cost of the procedure suggest that it should be considered as standard care to lower infant and maternal morbidity and mortality.