Identification of maternal opioid abuse in pregnancy is often difficult to ascertain in the absence of a reliable self-report. We aimed to characterize an at-risk neonatal population for opioid exposures as well as other drugs of abuse and alcohol. From June 2007 to January 2009, 563 neonatal hair and 1318 meconium specimens were assessed for opioids and were positive in 11.4% and 17.0%, respectively. Neonates testing positive for opioids in hair or meconium analysis were also more likely to test positive for other licit and illicit substances (odds ratiohair, 1.75; 95% confidence interval, 1.03-2.97; odds ratiomeconium, 1.61; 95% confidence interval, 1.16-2.22). Specifically, a positive neonatal hair test for opioids also predicted a positive result for oxycodone. In addition, a positive meconium test result for opioids was associated with positive results for cocaine, oxycodone, methadone, benzodiazepines, and fatty acid ethyl esters (alcohol). Finally, there was a significant correlation between maternal and neonatal hair test results for opioids (Spearman rank rho = 0.657, P = 0.03). Understanding the addiction profiles of these women may lead to better clinical and social management and may largely benefit an at-risk population.