UNLABELLED: The risk for misuse of opioid medications is a significant challenge in the management of chronic pain. The identification of those who may be at greater risk for misusing opioids is needed to facilitate closer monitoring of high-risk subgroups, and may help to identify therapeutic targets for mitigating this risk. The aim of this study was to examine whether distress intolerance-the perceived or actual inability to manage negative emotional and somatic states-was associated with opioid misuse in those with chronic pain. A sample of 51 participants prescribed opioid analgesics for chronic back or neck pain were recruited for a 1-time laboratory study. Participants completed measures of distress intolerance and opioid misuse, and a quantitative sensory testing battery. Results suggested that distress intolerance was associated with opioid misuse, even controlling for pain severity and negative affect. Distress intolerance was not associated with pain severity, threshold, or tolerance, but was associated with self-reported anxiety and stress after noxious stimuli. This study found robust differences in distress intolerance between adults with chronic pain with and without opioid medication misuse. Distress intolerance may be a relevant marker of risk for opioid misuse among those with chronic pain. PERSPECTIVE: This study demonstrated that distress intolerance was associated with opioid misuse in adults with chronic pain who were prescribed opioids. Distress intolerance can be modified with treatment, and thus may be relevant not only for identification of risk for opioid misuse, but also for mitigation of this risk.