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The use of chronic opioid therapy for pain management has increased dramatically without adequate study of potential deleterious effects on breathing during sleep. We conducted a retrospective cohort study comparing 60 patients taking chronic opioids matched with non-opioid patients for age, gender, and body mass index to determine the effect of morphine dose equivalent on breathing patterns during sleep. The apnea/hypopnea index was greater in the opioid group (43.5/hour vs. 30.2/ hour, pϽ.05). The difference was due to increased central apneas in the opioid group (12.8/hour vs. 2.1/hour; pϽ.001). Arterial oxygen saturation in the opioid group was significantly lower during both wakefulness (difference 2.1%, p Ͻ.001) and NREM sleep (difference 2.2%, pϽ.001) but not REM sleep (difference 1.2%) than the non-opioid group. Within the opioid group, and after controlling for body mass index, age, and gender, there was a dose response relationship between morphine dose equivalent and ataxic breathing (pϽ.02), apnea/hypopnea (pϽ.001), obstructive apnea (pϽ.001), hypopnea (pϽ.001) and central apnea indices (pϽ.001). Body mass index was inversely related to apnea/hypopnea index severity in the opioid group. There is a dosedependent relationship between chronic opioid use and development of a unique pattern of respiration consisting of ataxic breathing and central sleep apneas, which can be profound and has not been previously described. These results indicate that chronic opioid use is an unrecognized and independent risk factor for unstable sleep-disordered breathing, which can cause significant disruption in normal ventilatory patterns. The assumption that tolerance to the respiratory depressant effects of opioids occurs with chronic administration is not entirely supported by this study.