BACKGROUND Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. OBJECTIVE To assess the effectiveness and safety of using an opiate compared to a sedative or non-pharmacological treatment for treatment of NAS due to withdrawal from opiates. METHODS The review was updated in 2010 with additional searches CENTRAL, MEDLINE and EMBASE supplemented by searches of conference abstracts and citation lists of published articles. METHODS Randomized or quasi-randomized controlled trials of opiate treatment in infants with NAS born to mothers with opiate dependence. METHODS Each author assessed study quality and extracted data independently. RESULTS Nine studies enrolling 645 infants met inclusion criteria. There were substantial methodological concerns in all studies comparing an opiate with a sedative. Two small studies comparing different opiates were of good methodology.Opiate (morphine) versus supportive care (one study): A reduction in time to regain birth weight and duration of supportive care and a significant increase in hospital stay was noted.Opiate versus phenobarbitone (four studies): Meta-analysis found no significant difference in treatment failure. One study reported opiate treatment resulted in a significant reduction in treatment failure in infants of mothers using only opiates. One study reported a significant reduction in days treatment and admission to the nursery for infants receiving morphine. One study reported a reduction in seizures, of borderline statistical significance, with the use of opiate.Opiate versus diazepam (two studies): Meta-analysis found a significant reduction in treatment failure with the use of opiate.Different opiates (six studies): there is insufficient data to determine safety or efficacy of any specific opiate compared to another opiate. CONCLUSIONS Opiates compared to supportive care may reduce time to regain birth weight and duration of supportive care but increase duration of hospital stay. When compared to phenobarbitone, opiates may reduce the incidence of seizures but there is no evidence of effect on treatment failure. One study reported a reduction in duration of treatment and nursery admission for infants on morphine. Compared to diazepam, opiates reduce the incidence of treatment failure. A post-hoc analysis generates the hypothesis that initial opiate treatment may be restricted to infants of mothers who used opiates only. In view of the methodologic limitations of the included studies the conclusions of this review should be treated with caution.