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The objectives of this study were to describe the longitudinal trends of pharmacological treatment initiation and persistence in adult patients with attention-deficit/hyperactivity disorder (ADHD) and to explore how patients' sociodemographic and clinical characteristics affect these patterns.A retrospective cohort of 23,747 adult patients with new ADHD episodes was assembled using Medicaid extract files of 29 US states from 1999 and 2010. Sociodemographic and clinical characteristics of treatment initiators and noninitiators, and treatment persistent and nonpersistent patients were compared using multivariable logistic regression.The overall treatment initiation and 1-year persistence rate was 22.5% and 34.2%, respectively. After adjustment, the propensity of initiating pharmacotherapy and being persistent tripled (2010 vs 2000; odds ratio, 3.25; 95% confidence interval, 2.61–4.04) and almost doubled (2009 vs 2000; odds ratio, 1.86; 95% confidence interval, 1.20–2.90) over the study period. Male, racial and ethnic minorities, and younger age groups had a decreased propensity for treatment initiation and persistence. The likelihood of initiating treatment was similar for rural and urban residents but varied among different US states. Severe mental comorbidities and, concordantly, use of antipsychotics or mood stabilizers reduced the propensity of treatment initiation but had little effect on persistence. Patients filling sustained release stimulants were most likely to be persistent. Finally, preexisting cardiovascular conditions reduced the likelihood of receiving treatment but were not associated with persistence.The propensity to initiate and persist on pharmacological treatment in adults with ADHD has increased in the last decade but remains low. Treatment patterns were closely related to several sociodemographic and clinical determinants. Our findings provide valuable information to ensure appropriate treatment choices for these patients.