Objective: To advance understanding of the effectiveness of evidence-based treatments for comorbid posttraumatic stress disorder (PTSD) and substance use disorder (SUD), research must provide a more nuanced picture of how substance use affects change in PTSD symptoms over the course of treatments and whether prolonged exposure techniques can be efficacious during active substance use. A data set that included patients with PTSD/subthreshold-PTSD and SUD treated with an exposure-based intervention provided an opportunity to conduct a secondary analysis to test how patients’ substance use impacted PTSD change over treatment. Method: We applied growth models to week-to-week PTSD symptom and substance use changes during treatment and follow-up of a randomized controlled trial of two cognitive– behavioral treatments for PTSD and SUD: Concurrent Treatment of PTSD and SUD Using Prolonged Exposure (COPE) and Relapse Prevention Therapy (RPT). Cross-lagged analyses were used to determine whether prior week substance use impacted subsequent PTSD symptom severity. Results: Both treatments evidenced significant reductions in PTSD symptom severity. In the context of continued substance use, results suggest that individuals still benefit from exposure-based treatment. Conclusion: Results provide evidence that RPT and COPE both led to significant reductions in PTSD, providing further support that exposure-based techniques tailored for SUD can be conducted without jeopardizing PTSD or SUD outcomes. Implications for clinical decision making around treatment selection are discussed.