Maternal tobacco consumption during pregnancy has been associated with lower birth weight infants, preterm births, intrauterine growth retardation, smaller head circumference and increase in morbidity, yet few studies have examined the role tobacco has on the opiate neonatal abstinence syndrome (NAS). This study examined the effect of prenatal tobacco exposure on NAS for infants born to mothers maintained on methadone during gestation. Twenty-nine pregnant women and their newborn infants participated in this study. Tobacco exposure was based on maternal self-report with 16 women reporting cigarette consumption of 10 or less per day and 13 reporting smoking 20 cigarettes or more a day. The onset, peak, and duration of NAS were examined. Results showed that infants born to mothers who reported smoking 20 or more cigarettes per day had significantly higher NAS peak scores of 9.8 versus 4.8, and took longer to peak (113.0 h versus 37.8 h), than light smokers of 10 or fewer cigarettes per day. We concluded that tobacco use in conjunction with methadone plays an important role in the timing and severity of NAS in prenatally exposed infants.