Context Maternal use of cocaine during pregnancy remains a significant public health problem, particularly in urban areas of the United States and among women of low socioeconomic status. Few longitudinal studies have examined cocaine-exposed infants, however, and findings are contradictory because of methodologic limitations. Objective To assess the effects of prenatal cocaine exposure on child developmental outcomes. Design Longitudinal, prospective, masked, comparison birth cohort study with recruitment in 1994-1996. Setting Obstetric unit of a large US urban teaching hospital. Participants Four hundred fifteen consecutively enrolled infants (218 cocaine-exposed and 197 unexposed) identified from a high-risk, low-socioeconomic status, primarily black (80%) population screened through clinical interview and urine and meconium samples for drug use. The retention rate was 94% at 2 years of age. Main Outcome Measures The Bayley Mental and Motor Scales of Infant Development, assessed at 6.5, 12, and 24 months of corrected age. Results Controlled for confounding variables, cocaine exposure had significant effects on cognitive development, accounting for a 6-point deficit in Bayley Mental and Motor Scales of Infant Development scores at 2 years, with cocaine-exposed children twice as likely to have significant delay (mental development index <80) (odds ratio, 1.98; 95% confidence interval, 1.21-3.24; P=.006). For motor outcomes, there were no significant cocaine effects. Conclusions Cocaine-exposed children had significant cognitive deficits and a doubling of the rate of developmental delay during the first 2 years of life. Because 2-year outcomes are predictive of later cognitive outcomes, it is possible that these children will continue to have learning difficulties at school age.