ABSTRACT: IMPORTANCE:Current information on the prevalence and sociodemographic and clinical profiles of individuals in the general population with DSM-5 drug use disorder (DUD) is limited. Given the present societal and economic context in the United States and the new diagnostic system, up-to-date national information is needed from a single uniform data source. OBJECTIVE:To present nationally representative findings on the prevalence, correlates, psychiatric comorbidity, disability, and treatment of DSM-5 DUD diagnoses overall and by severity level. DESIGN, SETTING, AND PARTICIPANTS:In-person interviews were conducted with 36,309 adults in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III, a cross-sectional representative survey of the United States. The household response rate was 72%; person-level response rate, 84%; and overall response rate, 60.1%. Data were collected April 2012 through June 2013 and analyzed from February through March 2015. MAIN OUTCOMES AND MEASURES:Twelve-month and lifetime DUD, based on amphetamine, cannabis, club drug, cocaine, hallucinogen, heroin, nonheroin opioid, sedative/tranquilizer, and/or solvent/inhalant use disorders. RESULTS:Prevalences of 12-month and lifetime DUD were 3.9% and 9.9%, respectively. Drug use disorder was generally greater among men, white and Native American individuals, younger and previously or never married adults, those with lower education and income, and those residing in the West. Significant associations were found between 12-month and lifetime DUD and other substance use disorders. Significant associations were also found between any 12-month DUD and major depressive disorder (odds ratio [OR], 1.3; 95% CI, 1.09-1.64), dysthymia (OR, 1.5; 95% CI, 1.09-2.02), bipolar I (OR, 1.5; 95% CI, 1.06-2.05), posttraumatic stress disorder (OR, 1.6; 95% CI, 1.27-2.10), and antisocial (OR, 1.4; 95% CI, 1.11-1.75), borderline (OR, 1.8; 95% CI, 1.41-2.24), and schizotypal (OR, 1.5; 95% CI, 1.18-1.87) personality disorders. Similar associations were found for any lifetime DUD with the exception that lifetime DUD was also associated with generalized anxiety disorder (OR, 1.3; 95% CI, 1.06-1.49), panic disorder (OR, 1.3; 95% CI, 1.06-1.59), and social phobia (OR, 1.3; 95% CI, 1.09-1.64). Twelve-month DUD was associated with significant disability, increasing with DUD severity. Among respondents with 12-month and lifetime DUD, only 13.5% and 24.6% received treatment, respectively. CONCLUSIONS AND RELEVANCE:DSM-5 DUD is a common, highly comorbid, and disabling disorder that largely goes untreated in the United States. These findings indicate the need for additional studies to understand the broad relationships in more detail; estimate present-day economic costs of DUDs; investigate hypotheses regarding etiology, chronicity, and treatment use; and provide information to policy makers about allocation of resources for service delivery and research. Findings also indicate an urgent need to destigmatize DUD and educate the public, clinicians, and policy makers about its treatment to encourage affected individuals to obtain help.