Universal urine testing for cocaine, amphetamines, and opiates was performed on 1643 women admitted to an obstetric service for a 1-year period with 20.5% having positive results. There were 299 patients with positive toxicology results matched for race and discharge date with patients having negative toxicology and drug history. Significant differences in age, prior obstetric history, prenatal care, alcohol history, and smoking were noted between groups. There was a significant decrease in birth weight, head circumference, length, and gestational age for the drug-positive group, which was most marked in cocaine and multiple drug users. These differences persisted after we controlled for smoking, prenatal care, and prior preterm births. Differences in birth weight and head circumference remained after we controlled for gestational age. Rates of congenital anomalies and abruptio placental were similar between groups. Perinatal substance abuse is independently associated with growth retardation and prematurity. Multiple risk factors are frequently present, necessitating a comprehensive approach to prenatal care.