The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of ≥34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had ≥10 μg/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of <2 μg/mL. A vaccine that induces IgG anti-GBS type III levels of ≥10 μg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen.