OBJECTIVES: Opioid abuse and overdose is a major public health issue in the United States. Accordingly, the purpose of this review is to compare the impact of opioid abuse treatments (methadone, buprenorphine, buprenorphine-naloxone, naloxone, and naltrexone) on mortality and healthcare utilization. METHODS: A systematic literature review was performed in Fall 2016 using PubMed, PsychINFO, IPA, and CINAHL according to PRISMA guidelines. Outcomes of interest included opioid overdose mortality and healthcare utilization rates. Study eligibility was determined by two reviewers in an un-blinded and standardized manner. English-language studies utilizing a quasi-experimental or experimental design in a sample of U.S. adults at least 18 years of age were eligible for review. Additional inclusion criteria consisted of: prescription or nonprescription opioid use in the study sample; provision of methadone, buprenorphine, buprenorphine-naloxone, naloxone, or naltrexone; and a measure of suspected opioid overdose death or healthcare utilization rates. RESULTS: Eleven eligible full-text articles were identified over the period of 1998 to 2016. Sample sizes varied from 25 to over 8,000, with 5 observational and 6 experimental study designs. Five articles addressed opioid overdose mortality only, 5 examined healthcare utilization rates only, and one assessed both overdose mortality and healthcare utilization. Only one study directly compared two opioid dependence medications (buprenorphine-containing products versus methadone); 10 studies used counseling or no treatment (usual care) as the comparator. Buprenorphine and buprenorphine-naloxone resulted in a lower number of ambulatory care visits at 6 months compared to methadone (mean difference=-71, p< 0.0001). Overdose mortality and healthcare utilization rates were lower across all treatments compared to usual care. No appreciable risks of bias were found. CONCLUSIONS: All treatments illustrated benefits in terms of overdose mortality and healthcare utilization rates, but buprenorphine-containing treatments may be associated with lower healthcare utilization rates compared to methadone. Additional comparative studies are needed.