OBJECTIVES: To compare 6-month medical costs and hospitalization risk of adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) receiving extended-release methylphenidate (OROS-MPH, CONCERTA®) to those receiving mixed amphetamine salts extended release (MAS-XR, Adderall XR®) or atomoxetine (Strattera®) from employer perspective. METHODS: We examined data from a U.S. employer claims database of 5 million beneficiaries (1999-2004). Analysis was restricted to adults aged 18-64 with at least one diagnosis of ADHD (ICD-9: 314.x) and at least one prescription of OROS-MPH, MAS-XR, or atomoxetine. Adults were required to have continuous eligibility 6 months before and after their latest therapy initiation and have no ADHD therapy in the prior 6 months. Descriptive measures of medical costs (including outpatient and inpatient costs) and hospitalization risk were computed over 6 months following therapy initiation. Generalized estimating equations (GEE) models were used to compare costs of adults receiving alternative therapies adjusting for baseline demographic characteristics, substance abuse, depression, and the Charlson comorbidity index. Costs were adjusted to 2004 dollars using medical CPI. RESULTS: Of the research sample (n=4569), 31.8% received OROS-MPH, 34.0% MAS-XR, and 34.2% atomoxetine. In the 6-month follow-up period, medical costs were $1251 for OROS-MPH, $1422 for MAS-XR, and $1581 for atomoxetine-treated adults. The GEE model adjusting for patient characteristics found that 6-month medical costs for OROS-MPH-treated adults were $141 less than for the MAS-XR-treated (p=0.02) and $132 less than for the atomoxetine-treated (p=0.03). The risk of having at least one hospitalization was 42% higher for adults treated with MAS-XR (OR=1.42, 95% CI: 0.99-2.05) and 51% higher for adults treated with atomoxetine (OR=1.51, 95% CI: 1.05-2.17) compared to adults treated with OROS-MPH. CONCLUSIONS: Over the 6-month period after therapy initiation, adults treated with OROS-MPH had lower medical costs than those treated with MAS-XR and lower medical costs and risk of hospitalization than adults treated with atomoxetine.