Although there are high rates of abstinence among American Indians (AIs), there also is evidence of alcohol and drug use disorders disproportionately affecting Native communities. As a result of generations of systemic racism and historical trauma, AIs experience serious health disparities associated with substance use disorders (SUDs). Effective treatments for SUD are critically needed for improving health equity in AI communities, but there are few culturally grounded evidence-based interventions developed or tested with AIs. With this study, Randomized Controlled Trial of Indigenous Recovery Planning for American Indians, we aim to help fill this gap. Our research uses a Community-Based Participatory Research (CBPR) framework to test the efficacy of a culturally adapted relapse prevention intervention designed collaboratively by community partners from the Fort Peck Indian Reservation in northeastern Montana and research partners from Montana State University. Indigenous Recovery Planning (IRP) employs trained Fort Peck community members to deliver manualized intervention content culturally adapted from Relapse Prevention (RP), one of the most studied and efficacious treatments for SUD. Using data from 4 mixed-methods preliminary studies, we have worked closely with a Community Advisory Board (CAB) to modify RP to focus on strengths, increase levels of protective factors, address culturally specific risk factors, and overcome barriers to engagement in treatment. We now will test the efficacy of IRP in a prospective randomized controlled trial with 150 tribal members with SUD using a waitlist control group, a design desired by the community partners. Using random assignment to IRP (immediate intervention; n = 75) or to a waitlist control group (delayed intervention; n = 75), we will test the effects of IRP on primary outcomes (percent days abstinent) and secondary outcomes (substance-related consequences, quality of life) assessed post-intervention. We also will examine maintenance of changes in treatment outcomes at 12-week post-intervention follow-up, and examine hypothesized culturally specific mediators of treatment effects (AI identity, spirituality, communal mastery, grief and loss, distress from historical trauma, lateral violence, and racism) identified in our preliminary studies. Finally, we will conduct a process evaluation to examine the acceptability and sustainability of the intervention to ensure that IRP addresses barriers to evidence-based SUD interventions as designed. This research will fill an important gap in scientific knowledge regarding the efficacy and acceptability of culturally adapted evidence-based treatments tested in AI populations. This knowledge may be transferable to other communities with similar cultural values and barriers to treatment. By increasing access to efficacious treatment, this research has the potential to improve health outcomes and decrease SUD-related health disparities for underserved AI commun...