OBJECTIVES The buprenorphine/naloxone (BUP/NAL) combination is used in the treatment of prescription opioid dependence (OPD). The objective of this study was to determine if there were health economic advantages related to treatment compared to no pharmacological treatment. METHODS A retrospective cohort analysis was performed using insurance claims extracted from the US Truven Health MarketScan® Medicaid database from January 2007 to December 2012. Two groups were considered: 1) patients with opioid prescription drug (OPD) dependence treated with buprenorphine/naloxone and 2) patients with opioid prescription drug (OPD) dependence and no pharmacological treatment. Final study groups were selected with one-to-one matching on demographic characteristics, comorbidities at baseline and cost of outpatient and inpatient care over six months before index date. Resource use (pharmacy claims, outpatient claims, emergency room admission and hospital admission) and corresponding costs over twelve months after index date were compared between groups. RESULTS Each group included 362 patients. Patient characteristics at baseline, resource use, and healthcare costs before index date were comparable between the two groups. At   twelve months after the index date, patients with no pharmacological treatment had higher resource utilization in every category but medication. Total costs over 12 months were $14,983 and $15,692 in groups with and without pharmacological treatment, respectively (p = 0.67). Patients with pharmacological treatment had a higher pharmacy cost, but this was offset by the higher cost of outpatient visits in patients with no pharmacological treatment. These visits were mostly related to mental disorders, nervous system, skin and musculoskeletal disorders and injuries and poisonings. CONCLUSIONS While the treatment of opioid dependence with buprenorphine/naloxone is associated with higher medication acquisition cost, it is outweighed by cost savings in other categories, especially  outpatient care. Patients without pharmacological treatment use more healthcare resources and have higher total costs.