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To determine factors influencing intrapartum antibiotic prophylaxis (IAP) failure in the prevention of group B streptococcus (GBS) early-onset disease (EOD).GBS EOD case is defined as isolation of GBS from a normally sterile body site (e.g. blood or cerebrospinal fluid) in infants aged ≤7 days. During a consecutive 93-month period, GBS EOD cases and care data were reviewed.Seventy-nine GBS EOD cases were registered; 67 infants were born to women who received no i.v. antibiotics during labor. The 12 EOD cases exposed to IAP were more likely to be associated with emergency caesarean section (p = 0.0015), maternal obstetric risk factors (ORFs) (p = 0.0061), particularly intrapartum fever (p = 0.0002), and to present with signs of illness at birth (p = 0.0015). Correct dosages, agents, and timing were registered in three cases only; of which two were associated with intrapartum fever.ORFs, emergency caesarean section, and signs of illness at birth are significantly associated with GBS EOD in infants exposed to IAP. This study also suggests that recommended IAP agents, dosages, and timing are infrequently associated with EOD. Strict protocol adherence is recommended in all cases.