BACKGROUND: Among opioid-treated chronic pain patients, deficient response inhibition in the context of emotional distress may contribute to maladaptive pain coping and prescription opioid misuse. Interventions that aim to bolster cognitive control and reduce emotional reactivity (e.g., mindfulness) may remediate response inhibition deficits, with consequent clinical benefits. PURPOSE: To test the hypothesis that a mindfulness-based intervention, Mindfulness-Oriented Recovery Enhancement (MORE), can reduce the impact of clinically relevant, negative affective interference on response inhibition function in an opioid-treated chronic pain sample. METHODS: We examined data from a controlled trial comparing adults with chronic pain and long-term prescription opioid use randomized to either MORE (n = 27) treatment or to an active support group comparison condition (n = 30). Participants completed an Emotional Go/NoGo Task at pre- and post-treatment, which measured response inhibition in neutral and clinically relevant, negative affective contexts (i.e., exposure to pain-related visual stimuli). RESULTS: Repeated-measures analysis of variance indicated that compared with the support group, participants in MORE evidenced significantly greater reductions from pre- to post-treatment in errors of commission on trials with pain-related distractors relative to trials with neutral distractors, group × time × condition F(1,55) = 4.14, p = .047, η2partial = .07. Mindfulness practice minutes and increased nonreactivity significantly predicted greater emotional response inhibition. A significant inverse association was observed between improvements in emotional response inhibition and treatment-related reductions in pain severity by 3-month follow-up. CONCLUSIONS: Study results provide preliminary evidence that MORE enhances inhibitory control function in the context of negative emotional interference.