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Escalating rates of prescription opioid use and abuse have occurred in the context of efforts to improve the treatment of nonmalignant pain.The aim of the study was to characterize the diagnosis and management of nonmalignant pain in ambulatory, office-based settings in the United States between 2000 and 2010.Serial cross-sectional and multivariate regression analyses of the National Ambulatory Medical Care Survey (NAMCS), a nationally representative audit of office-based physician visits, were conducted.(1) Annual visit volume among adults with primary pain symptom or diagnosis; (2) receipt of any pain treatment; and (3) receipt of prescription opioid or nonopioid pharmacologic therapy in visits for new musculoskeletal pain.Primary symptoms or diagnoses of pain consistently represented one-fifth of visits, varying little from 2000 to 2010. Among all pain visits, opioid prescribing nearly doubled from 11.3% to 19.6%, whereas nonopioid analgesic prescribing remained unchanged (26%–29% of visits). One-half of new musculoskeletal pain visits resulted in pharmacologic treatment, although the prescribing of nonopioid pharmacotherapies decreased from 38% of visits (2000) to 29% of visits (2010). After adjusting for potentially confounding covariates, few patient, physician, or practice characteristics were associated with a prescription opioid rather than a nonopioid analgesic for new musculoskeletal pain, and increases in opioid prescribing generally occurred nonselectively over time.Increased opioid prescribing has not been accompanied by similar increases in nonopioid analgesics or the proportion of ambulatory pain patients receiving pharmacologic treatment. Clinical alternatives to prescription opioids may be underutilized as a means of treating ambulatory nonmalignant pain.