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The 2-year posttreatment course of substance abuse patients with posttraumatic stress disorder (PTSD) was examined in a multisite evaluation of Veterans Affairs substance abuse treatment. Substance abuse patients with PTSD (SUD-PTSD) were compared with patients with only substance use disorder (SUD only) and patients with other comorbid psychiatric diagnoses (SUD-PSY) on outcomes during the 2 years after treatment. SUD-PTSD patients had a poorer long-term course on substance use, psychological symptom, and psychosocial outcomes than SUD-only and SUD-PSY patients. Coping methods were examined as mediators of the effect of PTSD on substance use outcomes. Greater use of avoidance coping styles and less use of approach coping at 1 year partially accounted for the association of PTSD with 2-year substance use. Treatments that address multiple domains of functioning and focus on alternative coping strategies are recommended for this population.