Objective: To compare two protocols for intrapartum antibiotic prophylaxis (IAP) against neonatal group B streptococcal (GBS) sepsis, with respect to staff compliance, in a prospective cohort study in the obstetric units of a community hospital (A) and a university teaching hospital (B). Methods: Cohorts comprised about 500 women attending antenatal clinics at each hospital (total 1096). Women identified as GBS carriers at 26–32 weeks'gestation and those who had intrapartum clinical risk factors (CRF) were eligible for IAP. Compliance was defined as the proportion of women eligible for IAP who received it according to protocol–as determined by audit of case records–and compared between hospitals and according to indication. Results: Overall, 39% of women were eligible for IAP. Indications were GBS carriage alone (21%), CRF alone (13% ) and both (5% ). Compliance was similar for GBS carriers at both hospitals: 78% at Hospital A and 76% at Hospital B. However, because of the poor predictive value of screening before 32 weeks, only 65%of intrapartum GBS carriers actually received IAP. For women with CRF only, compliance was significantly lower at Hospital B than Hospital A (56 vs. 75%; p= 0.03). Conclusions: According to currently recommended protocols, about one-third of healthy women are eligible for intrapartum antibiotics to prevent neonatal GBS sepsis. In practice, antibiotics are often used inefficiently because of poor compliance with protocols and poor predictive values of selection criteria. Better implementation strategies should improve compliance, but GBS vaccines are needed to replace prophylactic antibiotic use, with its associated disadvantages.