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Background: Opioid pharmacotherapy plays an important role in the treatment of pregnant opioid-dependent women. Today the standard and most studied treatments for opioid use disorder in pregnancy are methadone or buprenorphine maintenance therapy. Naltrexone is also an option for medication-assisted treatment, but its use during pregnancy remains understudied. Objective: The purpose of this systematic review was to examine pregnancy and neonatal outcomes in naltrexone-treated women compared to women treated with buprenorphine or methadone. Methods: A systematic review of the literature was performed from October 2020 to March 2021 by searching all available abstracts through South College’s Digital Library, National Center for Biotechnology Information (NCBI), Medline Complete, and PubMed. Final selection of articles was dependent on full text review, adherence to inclusion and exclusion criteria, and consensus among three researchers. Seven articles were selected and assessed for quality with tools from the National Heart, Lung and Blood Institute. Data extraction was performed using a modified data extraction template from Dr. Kandi Pitchford. Each researcher performed an initial data extraction of their assigned articles with the created tool. Then the other two researchers reviewed and confirmed the data extraction results by consensus. Qualitative analysis was performed with the finalized data extraction for each article. The data was analyzed as a body of evidence, at a manifest and latent level. Manifest level findings were presented in text and a table. The results of the quality assessment were reported as a component of the manifest level findings. The latent level findings were presented by study and theme, based on the elements of the final articles. v Results: Database research produced seven articles including a total of 40 studies pertaining to the management of opioid use disorder during pregnancy using methadone, buprenorphine, or naltrexone maintenance therapy. The total number of neonates investigated was 3,300: 294 naltrexone exposed neonates (NEN), 1,847 buprenorphine exposed neonates (BEN), 1,050 methadone exposed neonates (MEN), and 109 neonates that were categorized as traditional therapy, meaning methadone or buprenorphine. The naltrexone group showed a decrease in the need for NAS treatment compared to the buprenorphine and methadone groups with only 7.7% of NEN over all the studies needing treatment versus 46% of BEN and 61% of MEN. The difference between the birth weights of NEN and BEN compared to MEN was significant;however, the difference between BEN and NEN was too narrow to make a conclusion without more data. Naltrexone demonstrated rates of congenital abnormalities comparable to buprenorphine and better than methadone. Naltrexone also showed drastic benefit regarding length of hospital stay for neonates compared to buprenorphine or methadone. Birth weight, head circumference, and gestational age were comparable between the groups. Conclusion: This review of the literature suggests that naltrexone is a viable treatment option for pregnant patients with OUD who choose to detoxify from opioids during pregnancy. The use of naltrexone was not associated with higher rates of negative birth outcomes when compared with methadone and buprenorphine exposed neonates