Most African countries do not initiate hepatitis B vaccination at birth. We conducted a non-randomized controlled trial comparing hepatitis B vaccination given at age 0, 6, and 14 weeks versus the current Côte d'Ivoire schedule of 6, 10, and 14 weeks. Pregnant women were enrolled at four health centers in Abidjan. At age 9 months, 0.5% of infants in both the birth and 6-week cohorts were positive for HBsAg and all were born to HBeAg-positive women. Among infants of HBeAg-positive mothers, 9 of 24 (37.5%) in the birth cohort and 10 of 17 (58.8%) in the 6-week cohort were HBsAg positive (adjusted OR, 2.7; 95% CI: 0.7-11.0). While both vaccine schedules prevented most cases of infant HBV transmission, both also had high failure rates among infants of HBeAg-positive mothers. African infants may benefit from a birth dose but additional studies are needed to verify this hypothesis.