PROJECT ABSTRACT Nearly 90% of individuals with OUD report lifetime trauma exposure and 33% meet criteria for PTSD. Patients with co-occurring PTSD and OUD are at significantly greater risk for poor substance use and mental health outcomes vs. those with OUD alone. Although Prolonged Exposure (PE) therapy is a first-line treatment for PTSD, its efficacy is commonly undermined by poor attendance. We recently demonstrated the initial feasibility of a novel PE protocol for improving therapy attendance and PTSD symptoms among individuals maintained on MOUD. Participants were randomly assigned to: (a) Treatment as usual (TAU) (b) Prolonged Exposure therapy (PE) or (c) PE with attendance contingent financial incentives (PE+). Our results demonstrated the initial efficacy of PE+, as PE+ participants attended significantly more therapy sessions than PE participants and experienced significant improvements in PTSD symptoms. Our findings also suggest that, rather than undermining patients’ stability with illicit drug use, PE may be associated with less illicit substance use than SUD treatment alone. In the proposed research, we seek to: a) conduct a more definitive evaluation of this novel PE intervention, b) utilize a novel telemedicine platform to reach underserved patients, and c) further investigate this promising initial data suggesting that PE therapy may also be associated with improvements in illicit drug use. Primary Aim: To evaluate the efficacy of a novel telemedicine-delivered PE protocol for improving therapy attendance and PTSD symptoms. We will conduct a parallel three-group RCT among 135 adults with PTSD who are maintained on MOUD (45 TAU, 45 PE, 45 PE+). All study visits will be conducted via telemedicine and attendance-contingent financial incentives will be delivered digitally. We hypothesize that participants assigned to PE+ will demonstrate greater PE session attendance and decreases in PTSD severity relative to those assigned to PE or TAU. Secondary Aims: (1) We will utilize rigorous and fine-grained assessment strategies to evaluate whether individuals receiving PE may actually experience reductions in their illicit opioid and other drug use. (2) We will conduct the first characterization of telemedicine-delivered PE acceptability and explore their association with PE treatment retention and PTSD symptom reduction. This study represents the first effort to examine the efficacy of PE delivered via telemedicine to individuals with OUD, and our investigative team is uniquely poised to disseminate our findings to improve clinical practice in real-world settings throughout the country.