This study investigated infant neurobehavioral functioning during the newborn period in 334 full-term, African American neonates (187 cocaine exposed, 147 non-cocaine exposed) enrolled prospectively at birth, with documentation of drug exposure status through maternal interview and urine and meconium toxicology assays. Infants were assessed using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) during the newborn period (0-6 postnatal days). Findings from multivariate profile analyses support a consistent, modest effect of prenatal cocaine exposure on neurobehavioral functioning in full-term neonates. All of the BNBAS cluster scores, with the exception of abnormal reflexes, were similarly affected, sharing a common slope (D=-0.14; 95% CI=-0.27, -0.003; P=.046) representing a -0.14 point difference between cocaine-exposed and non-cocaine-exposed infants after controlling for prenatal exposure to alcohol, tobacco, and marijuana (ATM); maternal age, education, employment, primigravida status, and prenatal care visits; and infant sex and postnatal age in days. Fetal growth was also related to neurobehavioral functioning and, in part, mediated the relationship between cocaine exposure and the BNBAS cluster scores. Cocaine exposure during each trimester similarly influenced infant neurobehavioral profiles, with cocaine-associated deficits most pronounced in infants with exposure in all three trimesters. Results from qualitative and quantitative urine and meconium bioassay indicators further substantiated these results. Findings, while significant, represent modest effect sizes in full-term infants.