IntroductionAmerican Indians and Alaska Native (AIAN) populations are disproportionately affected by opioid misuse. Medication for opioid use disorder (MOUD) is essential to decrease overdose events and overdose deaths. AIAN communities can benefit from MOUD programs that are housed within primary care clinics to improve treatment accessibility. This study aimed to gather information on the needs, barriers, and successes related to implementing MOUD programs in Indian health clinics (IHCs) offering primary care. MethodsThe study used the Reach, Effectiveness, Adoption, Implementation, and Maintenance Qualitative Evaluation for Systematic Translation (RE-AIM QuEST) evaluation framework to structure key informant interviews with clinic staff who received technical assistance for MOUD program implementation. The study incorporated RE-AIM dimensions into a semi-structured interview guide. We developed the coding approach for analyzing interview data using Braun and Clarke's (2006) reflexive thematic analysis in qualitative research. ResultsEleven clinics participated in the study. The research team conducted twenty-nine interviews with clinic staff. We found that inadequate education about MOUD, scant resources, and limited availability of AIAN providers adversely impacted reach. Challenges with integrating medical and behavioral care, patient-level barriers (e.g., rural conditions, geographical dispersion), and limited workforce capacity impacted MOUD effectiveness. Stigma at the clinic level was detrimental to MOUD adoption. Implementation was challenging due to a limited number of waivered providers, and the need for technical assistance and MOUD policies and procedures. Staff turnover and restricted physical infrastructure negatively influenced MOUD maintenance. ConclusionsClinical infrastructure should be strengthened. The integration of culture into clinic services must be embraced by staff to support MOUD adoption. Increased representation from AIAN clinical staff is needed to appropriately represent the population being served. Stigma at various levels must be addressed, and the multiple barriers that AIAN communities face must be considered in understanding MOUD program implementation and outcomes.