Early-onset neonatal group B streptococci infection occurs in two cases per 1000 live births in the United States and is associated with a mortality rate greater than 20%. Nearly 30% of infected infants have concomitant meningitis and half suffer permanent neurologic damage. Group B streptococci also account for at least 20% of postpartum metritis. The annual cost of group B streptococci infection in the United States is conservatively estimated at nearly 2000 neonatal deaths and greater than $500 million, excluding the costs of long-term neurologic handicaps. Intrapartum chemoprophylaxis with ampicillin is effective in curtailing transmission of group B streptococci from mother to infant. Methods have been developed to identify maternal colonization before delivery. We applied principles of decision analysis to evaluate cost-effectiveness of intrapartum screening for maternal group B streptococci colonization with various reported methods in cohorts of low- and high-risk women. In the United States intrapartum screening for group B streptococci is cost-effective and offers the potential to avert a significant number of neonatal deaths and postpartum infections.