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Prospective outcomes study involving patients with chronic disabling occupational spinal disorders (CDOSD) diagnosed with (n = 199) or without (n = 1124) postinjury opioid-dependence disorder (ODD), based on the Diagnostic and Statistical Manual of Mental Disorders–fourth edition cirteria.To determine whether prescription opioid dependence, assessed at the beginning of rehabilitation treatment, is associated with poorer treatment outcomes in patients with CDOSDs attending an interdisciplinary rehabilitation program.Controversy exists regarding the risk of iatrogenic ODD and treatment outcomes when long-term opioid therapy is used in the treatment of chronic nonmalignant pain conditions.A consecutive sample of patients with CDOSDs [n = 1323; mean (SD) length of disability = 18.8 (20.7) months] attending a tertiary referral center received intensive physical reactivation and pain/disability management interventions, based on a functional restoration model, including detoxification from opioids. One-year outcomes included return to work, work retention, healthcare utilization, new surgeries, recurrent injuries, and disability claim settlement.Prevalence of ODD in this CDOSD population on entering the rehabilitation program was 15%. Even after adjusting for relevant demographic factors and comorbid psychiatric disorders, opioid-dependent patients were 1.7 times [95% confidence interval (CI): 1.0, 2.7] less likely to return to work, 2 times (95% CI: 1.3, 3.0) less likely to retain work at the 1-year interview, and 1.7 times (95% CI: 1.2, 2.5) more likely to engage in healthcare utilization from new providers, compared with nonopioid-dependent patients.Iatrogenic prescription opioid dependence may be a risk factor for less successful long-term work and health outcomes, even after detoxification from opioids as part of an interdisciplinary functional rehabilitation program. Chronic prescription opioid dependence in this patient population is also associated with a significantly higher prevalence of comorbid psychiatric conditions, both axis I and II.