Introduction: Alcohol use disorder (AUD) is a chronic relapsing and highly comorbid disease. Patients suffering from AUD are frequently seen in the emergency department (ED) presenting intoxicated or in withdrawal. Brief interactions in the ED are often the only portal of entry to the healthcare system for many of these patients. Oral naltrexone and long acting injectable naltrexone are effective treatment options for AUD associated with decreased cravings, shorter length of hospital stay, and lower cost of healthcare utilization. This study's objective was to perform a systematic review of the literature evaluating initiation of naltrexone in the ED. Methods: Electronic searches of Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and CINAHL were conducted and reference lists were hand-searched. Randomized controlled trials (RCTs) comparing initiation of naltrexone in patients (≥18 years) to standard care in the ED were included. Two reviewers independently screened titles and abstracts, reviewed full text articles for inclusion, assessed quality of the studies, and extracted data. Results: The search strategy yielded 183 potentially relevant citations. After eliminating duplicate citations and studies that did not meet eligibility criteria, 10 articles were retrieved for full text review. There were no published RCTs that examined naltrexone initiation in the ED. There is one ongoing study being conducted in New York, which aims to assess naltrexone initiation in the ED and measure health outcomes and quality of life of study participants, as well as potential healthcare cost savings. Conclusion: The lack of published research in this area demonstrates a significant gap in knowledge. It is clear that well-designed RCTs are needed to evaluate the effectiveness of initiating naltrexone for those with AUD at the ED visit.