To determine whether maternal cocaine use at the time of delivery of the infant is an independent risk factor for low birth weight or prematurity, we performed a prospective anonymous urine toxicology screening study among 425 women in a large urban university-based maternity hospital. The data were subjected to univariate analysis with the Fisher Exact Test and odds ratio determination, and to multivariate analyses by logistic regression. Of 11 variables analyzed, cocaine use near delivery, no prenatal care, marijuana and cigarette use, black race, a previous preterm infant, and staff service were significantly associated with premature birth by univariate analysis. No prenatal care (odds ratio, 9.89; 95% confidence intervals, 3.74 to 26.17) and cocaine use (odds ratio, 7.31; 95% confidence intervals, 2.87 to 18.61) demonstrated the greatest risk associated with premature birth by univariate prediction. After analysis by multivariate logistic modeling, only cocaine use detected at birth remained a significant predictor of prematurity (odds ratio, 13.4; 95% confidence intervals, 1.23 to 145.0). Staff service, black race, cocaine use near the time of delivery, marijuana and cigarette use, a previous preterm infant, and no prenatal care were significant univariate predictors of low birth weight. Cocaine use (odds ratio, 4.14; 95% confidence intervals, 1.18 to 14.56) and marijuana use (odds ratio, 4.52; 95% confidence intervals, 1.42 to 14.39) were the strongest univariate factors. After analysis by multivariate logistic modeling, cocaine use near the time of delivery demonstrated the highest odds ratio (9.90) for predicting low birth weight, but the 95% confidence intervals included 1 (0.53 to 184.0). We conclude that independent of potentially interrelated covariables, a positive result on a cocaine urine toxicology test at the time of delivery is the most dominant factor that was tested to predict prematurity and possibly low birth weight. The effect of cocaine on the duration of gestation or fetal growth may be due to its pharmacologic properties, or cocaine use during pregnancy may identify a subgroup of women whose risk is due to as-yet-unidentifiable socioeconomic or cultural characteristics.