American Indian/Alaska Native (AI/AN) populations face long-standing disparities across numerous health indicators including disproportionately high rates of substance abuse, a particularly damaging problem which impacts not only physical and mental health, but also community capacity and cultural connectedness. To address these disparities and the ongoing problem of access to appropriate treatment services, culturally relevant, evidence-based interventions must be developed and successfully disseminated. Urban AI/AN (i.e., those who live off Tribal land in urban centers) have more severe substance use problems and encounter unique barriers to treatment. For example, the majority of Indian-managed substance abuse treatment facilities are located in rural areas (60%), yet 78% of AI/AN reside in urban areas. Given these disparities in disease and treatment access, a web-delivered culturally congruent intervention could be a means of improving treatment outcomes among urban AI/AN. Web-based interventions can address challenges to adoption and implementation, enhance accessibility to and intensity of treatment, and improve outcomes. The investigative team completed a mixed methods acceptability study of an efficacious web-based version of the Community Reinforcement Approach (CRA) (plus contingency management [CM]) called the Therapeutic Education System (TES) (Bickel et al., 2008; Campbell et al., 2014) with urban AI/AN from programs in NIDA’s Clinical Trials Network (CTN). Results demonstrated high acceptability for core TES content delivered via computer but also that cultural adaptation would be highly desirable. Research supports culturally-informed interventions for AI/AN. Although urban AI/AN are heterogeneous with regard to tribal affiliation (i.e., language, history cultural activities), many similarities and consistencies in culture, values, and traditions exist. A cultural adaptation of TES for urban AI/AN (TES-NAV) was recently completed with supplemental CTN support. Building upon this developmental work, the goal of the current proposal is to evaluate the preliminary efficacy of TES-NAV to determine whether a future large-scale effectiveness trial is warranted. Specifically, a Stage IB randomized controlled trial among urban AI/AN (N=80) attending outpatient addiction treatment services will be conducted to (1) estimate preliminary effect size of 12 weeks of TES-NAV; (2) explore relevant moderators of TES-NAV outcomes and potential mechanisms of action; and (3) assess cultural factors that may correspond to variation in outcome. A three-month post-treatment follow-up will facilitate identification and interpretation of outcomes. This work follows the tenets of the Community Based Participatory Research approach and is guided by a long-standing collaborative board. In the final months of the project, the Board and other stakeholders will work with the investigative team to interpret findings and build consensus for next steps. The proposed study represents an important commitment to improving longstanding health disparities and is, to our knowledge, the first randomized controlled trial of a culturally adapted web-based addiction treatment for AI/AN.