We estimated childhood risk of developing selected DSM-IV Disorders, including Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Separation Anxiety Disorder (SAD), in children with prenatal cocaine exposure (PCE). Children were enrolled prospectively at birth (n = 476) with prenatal drug exposures documented by maternal interview, urine and meconium assays. Study participants included 400 African-American children from the birth cohort, 208 cocaine-exposed (CE) and 192 non-cocaine-exposed (NCE), who attended a 5-year follow-up assessment and whose caregiver completed the Computerized Diagnostic Interview Schedule for Children. Under a generalized linear model (logistic link), Fisher's exact methods were used to estimate the PCE-associated relative risk (RR) of these disorders. Our results indicated a modest but statistically robust elevation of ADHD risk associated with increasing levels of PCE (p less than 0.05). Binary comparison of CE versus NCE children indicated no PCE-associated RR. Estimated cumulative incidence proportions among CE children were 2.9% for ADHD (vs 3.1% NCE); 1.4% for SAD (vs 1.6% NCE); and 4.3% for ODD (vs 6.8% NCE). Our findings suggest evidence of increased risk of ADHD (but not ODD or SAD) in relation to an increasing gradient of PCE during gestation.