BACKGROUND: Individuals who use illicit substances exhibit cue-elicited craving and autonomic cue-reactivity when exposed to cues associated with past drug use. However, little is known about this phenomenon among chronic pain patients on long-term opioid therapy (LTOT). Negative cognitive-emotional reactivity in general (e.g., distress) and cognitive-emotional reactivity specific to pain (e.g., pain catastrophizing) might drive cue-reactivity independent of pain severity. Here we examined emotional distress and pain catastrophizing as predictors of cue-reactivity among a sample of chronic pain patients receiving LTOT. We also tested whether associations between distress, catastrophizing, and cue-reactivity differed as a function of opioid misuse status. MATERIALS AND METHODS: Patients receiving LTOT (N = 243) were classified as exhibiting aberrant behavior consistent with opioid misuse (MISUSE+, n = 145) or as using opioids as prescribed (MISUSE-, n = 97). Participants completed assessments of pain catastrophizing and emotional distress and then participated in an opioid cue-reactivity task one week later. Cue-elicited opioid craving and autonomic cue-reactivity were measured with craving ratings and high-frequency heart rate variability (HRV), respectively. RESULTS: Distress and catastrophizing predicted cue-elicited craving and HRV, whereas pain severity did not. Misuser status moderated the relationship between emotional distress and self-reported craving, such that higher levels of distress predicted craving among the MISUSE+ group, but not among the MISUSE- group. No moderating effects were found for catastrophizing. CONCLUSIONS: Findings suggest that although opioids are prescribed for analgesia, the exacerbating influence of negative cognitive-emotional reactivity, both in general and specific to pain, on cue-elicited opioid craving extends beyond the effects of pain severity alone.