HIV incidence continues to increase in Eastern Europe and Central Asia (EECA), in large part due to non-sterile injection drug use, especially within prisons. Therefore, medication-assisted therapy with opioid agonists is an evidence-based HIV-prevention strategy. The Kyrgyz Republic offers methadone within its prison system, but uptake remains low. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a framework for identifying people who would potentially benefit from methadone, intervening to identify OUD as a problem and methadone as a potential solution, and providing referral to methadone treatment. Using an SBIRT framework, we screened for OUD in Kyrgyz prisons among people who were within six months of returning to the community (n = 1118). We enrolled 125 people with OUD in this study, 102 of whom were not already engaged in methadone treatment. We conducted a pre-release survey followed by a brief intervention (BI) to address barriers to methadone engagement. Follow-up surveys immediately after the intervention and at 1 month, 3 months, and 6 months after prison release assessed methadone attitudes and uptake. In-depth qualitative interviews with 12 participants explored factors influencing methadone utilization during and after incarceration. Nearly all participants indicated favorable attitudes toward methadone both before and after intervention in surveys; however, interest in initiating methadone treatment remained very low both before and after the BI. Qualitative findings identified five factors that negatively influence methadone uptake, despite expressed positive attitudes toward methadone: (1) interpersonal relationships, (2) interactions with the criminal justice system, (3) logistical concerns, (4) criminal subculture, and (5) health-related concerns.