The co-occurrence of posttraumatic stress disorder (PTSD) and substance use disorders (SUD) is highly prevalent and difficult-to-treat. Mindfulness, defined as nonjudgmental attention to and awareness of present-moment experiences, represents a targetable mechanism with potential to predict and improve treatment outcomes for PTSD/SUD populations. We hypothesized that greater self-reported mindfulness at baseline (pre-treatment) would predict (a) lower end-of-treatment PTSD severity and (b) greater longest sustained abstinence during a 12-week cognitive-behavioral treatment program. Participants included 53 inner-city adults meeting at least four current symptoms of DSM-5 PTSD and current (DSM-IV) substance dependence (51% women; 75.5% African American; Mage = 45.42, SD = 9.99). Hierarchical regression analysis results indicated that higher levels of baseline mindfulness predicted lower end-of-treatment PTSD severity but not longest sustained abstinence from the primary substance of choice. Post hoc exploration of end-of-treatment PTSD symptom clusters indicated that higher baseline mindfulness predicted lower intrusion, negative alterations in cognitions and mood, and arousal and reactivity symptoms but not avoidance symptoms. Clinical and research implications are discussed.