This clinical policy from the American College of Emergency Physicians addresses key issues in opioid management in adult patients presenting to the emergency department. A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the following clinical questions: (1) In adult patients experiencing opioid withdrawal, is emergency department-administered buprenorphine as effective for the management of opioid withdrawal compared with alternative management strategies? (2) In adult patients experiencing an acute painful condition, do the benefits of prescribing a short course of opioids on discharge from the emergency department outweigh the potential harms? (3) In adult patients with an acute exacerbation of noncancer chronic pain, do the benefits of prescribing a short course of opioids on discharge from the emergency department outweigh the potential harms? (4) In adult patients with an acute episode of pain being discharged from the emergency department, do the harms of a short concomitant course of opioids and muscle relaxants/sedative-hypnotics outweigh the benefits? Evidence was graded and recommendations were made based on the strength of the available data.