Background: Naltrexone may provide a suitable alternative to methadone and buprenorphine in the treatment of pregnant opioid-dependent women; however, little is known about its effects on neonatal morbidity and mortality. Objective: The aim was to evaluate the health of neonates exposed to naltrexone in utero, and compare it with outcomes in neonates exposed to methadone or buprenorphine and a non-exposed control group. Methods: Sequential cohorts of Western Australian (WA) opioid-dependent women treated with implant naltrexone, oral methadone or sublingual buprenorphine were identified via records from a drug and alcohol clinic (Subiaco, WA) for naltrexone and state prescribing records for methadone and buprenorphine. A control cohort of non-opioid-dependent women was obtained from the WA electoral roll. Identifying information and treatment records for these women were linked against the Midwife Notification System records to identify exposed offspring born between 2001 and 2011. Birth characteristics, congenital anomalies and perinatal mortality for all neonates were extracted from state records. Results: The birth characteristics of naltrexone-exposed neonates (n = 68) were superior to methadone-exposed neonates (n = 199) in terms of birth size (birth weight, head circumference and length), hospital length of stay (5.5 vs. 11.3 days), and rates of neonatal abstinence syndrome (NAS) (7.5 vs. 51.5%). Naltrexone-exposed neonates were generally not significantly different to buprenorphine-exposed neonates (n = 124), with the exception of significantly lower rates of NAS (7.5 vs. 41.8%) and shorter hospital length of stay (5.5 vs. 8.0 days) in naltrexone-exposed neonates. Compared with the control group of neonates (n = 569), naltrexone-exposed neonates were not significantly different in terms of overall rates of congenital anomalies, stillbirths and neonatal mortality; however, they were significantly smaller (3137.1 vs. 3378.0 g), spent more time in hospital following birth (5.5 vs. 4.3 days) and had higher rates of NAS (7.5 vs. 0.2%). Exposure of neonates to prenatal methadone was associated with a high incidence of neonatal mortality (2.0 vs. 0.2 per 100 live births) and congenital anomalies (10.6 vs. 4.4 per 100 births) compared with the control group. Rates of neonatal mortality and congenital abnormalities in buprenorphine-exposed neonates were not significantly different to the control group. Conclusions: The use of implant naltrexone during pregnancy was not associated with higher rates of negative birth outcomes compared with methadone- and buprenorphine-exposed neonates. Significantly, naltrexone and buprenorphine were not associated with the high rates of neonatal mortality or congenital anomalies seen in methadone-exposed neonates.