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The American College of Occupational and Environmental Medicine's guidelines have been updated to develop more detailed guidance for treatment of acute, subacute, chronic, and postoperative pain with opioids.Literature searches were performed using PubMed, EBSCO, Cochrane Review, and Google Scholar without publication date limits. Of 264,617 articles' titles screened and abstracts reviewed, 263 articles met inclusion criteria. Of these, a total of 157 were of high and moderate quality addressing pain treatment. Comprehensive literature reviews were accomplished with article abstraction, critiquing, grading, evidence table compilation, and guideline finalization by a multidisciplinary expert panel to develop evidence-based guidance.No quality evidence directly supports histories, physical examinations, and opioid treatment agreements, although they are thought to be important. No quality trials were identified showing superiority of opioids, compared with nonsteroidal anti-inflammatory and other medications for treatment of chronic, noncancer pain. The use of opioid-sparing treatments associated with lower doses of postoperative opioids is also associated with better long-term functional outcomes. Selective use of opioids is recommended for patients with acute and postoperative pain. Consensus recommendations also include consideration of carefully conducted trials of chronic opioid treatment for highly select patients with subacute and chronic pain and to maintenance opioid prescriptions only if documented objective functional gain(s) results. A strong and reproducible dose–response relationship identifies a recommended morphine equivalent dose limit of no more than 50 mg/day. Higher doses should be prescribed only with documented commensurately greater functional benefit(s), comprehensive monitoring for adverse effects, informed consent, and careful consideration of risk versus benefit of such treatment. Chronic opioid use should be accompanied by informed consent, a treatment agreement, tracking of functional benefits, drug screening, and attempts at tapering.