Substance use disorders and post-traumatic stress disorder (PTSD) often co-occur, along with depression and anger. Despite evidence that Prolonged Exposure Therapy is effective for individuals with co-occurring PTSD and SUD when PE is implemented alongside SUD treatment, clinicians have been reluctant to offer PE or other trauma-focused therapies to individuals with co-occurring PTSD and SUD because of the belief that increased emotional distress would be counter-therapeutic for individuals in early recovery. A widely held explanation for the high degree of comorbidity is that individuals with PTSD use substances to reduce or avoid painful and disturbing PTSD symptoms. This case study describes the implementation and outcome of PE therapy with a 32-year-old man who had been admitted to a residential substance use treatment program for Latino males. The client had a long history of polysubstance use and severe PTSD. The client was homeless and reported significant depressive and anger symptoms. Assessment of PTSD revealed that he was using heroin and cocaine to avoid painful memories of a traumatic event that had occurred several years prior to his admission to this treatment program. Because the client reported using these substances to reduce emotional distress, PE was chosen as the PTSD intervention. During PE Therapy the client reported no thoughts or urges to use substances and at discharge from residential treatment he reported no problems with PTSD or depression. The client maintained all gains at 1-year follow-up, when he also reported that he was working full time and had remained abstinent since he completed treatment.