Objective To estimate the relationship between maternal methadone dose and the incidence of neonatal abstinence syndrome (NAS). Study design We performed a retrospective cohort study of pregnant women treated with methadone for opiate addiction who delivered live-born neonates between 1996 and 2006. Four dose groups, on the basis of total daily methadone dose, were compared (<= 80 mg/d, 81-120 mg/d, 121-160 mg/d, and >160 mg/d). The primary outcome was treatment for NAS. Symptoms of NAS were objectively measured with the Finnegan scoring system, and treatment was initiated for a score >24 during the prior 24 hours. Results A total of 330 women treated with methadone and their 388 offspring were included. Average methadone dose at delivery was 117 +/- 50 mg/d (range, 20-340 mg/d). Overall, 68% of infants were treated for NAS. Of infants exposed to methadone doses <= 80 mg/d, 81-120 mg/d, 121-160 mg/d, and >160 mg/d, treatment for NAS was initiated for 68%, 63%, 70%, and 73% of neonates, respectively (P = .48). The rate of maternal illicit opiate abuse at delivery was 26%, 28%, 19%, and 11%, respectively (P = .04). Conclusion No correlation was found between maternal methadone dose and rate of NAS. However, higher doses of methadone were associated with decreased illicit opiate abuse at delivery. (J Pediatr 2010; 157: 428-33).