OBJECTIVE:We tested whether mindfulness de-couples the expected anxiogenic effects of distress intolerance on psychological and physiological reactivity to and recovery from an anxiogenic stressor among participants experimentally sensitized to experience distress. METHOD: N = 104 daily smokers underwent 18-hours of biochemically-verified smoking deprivation. Participants were then randomized to a 7-min analogue mindfulness intervention (present moment attention and awareness training; PMAA) or a cope-as-usual control condition; and subsequently exposed to a 2.5-min paced over breathing (hyperventilation) stressor designed to elicit acute anxious arousal. Psychological and physiological indices of anxious arousal (Skin Conductance Levels; SCL) as well as emotion (dys)regulation (Respiratory Sinus Arrhythmia; RSA) were measured before, during and following the stressor. RESULTS: We found that PMAA reduced psycho-physiological dysregulation in response to an anxiogenic stressor, as well as moderated the anxiogenic effect of distress intolerance on psychological but not physiological responding to the stressor among smokers pre-disposed to experience distress via deprivation. CONCLUSIONS: The present study findings have a number of theoretical and clinical implications for work on mindfulness mechanisms, distress tolerance, emotion regulation, and smoking cessation interventions.