While maternal antibiotic prophylaxis has greatly reduced early-onset group B streptococcal (GBS) disease in the United States, a GBS vaccine currently under development could potentially prevent additional GBS cases and preterm births. A decision analytic model was created to compare preventive strategies using adolescent, maternal (prenatal), or postpartum vaccination with selective chemoprophylactic strategies. The current practice of culture-based chemoprophylaxis was predicted to prevent 55% of early plus late-onset GBS infections. Maternal vaccination strategies were superior to current practice, preventing 68-69% of all GBS infections and 4% of very preterm births (<32 weeks gestation). The most effective adolescent vaccination strategy combined vaccination with culture-based chemoprophylaxis for all women and prevented 66% of all GBS infections. All other strategies were similar in efficacy to current practice or inferior. Maternal GBS vaccination is predicted to prevent more cases of neonatal GBS disease than current practice and would prevent approximately one in 25 very preterm births.