OBJECTIVE: One recommended target outcome of ADHD therapy is enhanced safety in the community. This study was designed to evaluate whether once-daily CONCERTA(r) extended-release (XR) methylphenidate (MPH) is associated with a lower accident/injury rate over a one-year period than three-times daily (TID) immediate-release (IR) MPH in children with attention deficit/hyperactivity disorder (ADHD). METHODS: Data for this analysis were derived from the IHCIS National Managed Care Benchmark Database. Criteria for inclusion in the analysis were: 1) age 6-12 years at date of first prescription for XR MPH or TID IR MPH (index date); 2) patient-level data files containing information for at least 6 months before and 12 months after the index date; 3) no ADHD medications in the 6-month period before the index date; 4) no XR MPH use by the IR MPH group in the 12-month follow-up period. The outcome variable was the number of children with either an outpatient or hospital claim related to an accident or injury. Multivariate regression analysis was performed to assess the influence of selected demographic and clinical variables on accident/injury rate. RESULTS: IR MPH: n = 344, mean age 9.6 years, 76% male; XR MPH: n = 1431, mean age 9.8 years, 75% male. XR MPH patients were less likely (p <0.0001) to discontinue medication (47.45% vs. 70.93%), less likely to switch to another ADHD medication (37.32% vs. 57.27%), and more likely to persist (i.e. no gaps >14 days between prescription fills) with treatment (11.67% vs. 1.74%). Children initially receiving XR MPH were less likely to experience an accident/injury in the 12-month follow-up period compared to those receiving IR MPH (OR = 0.58, 95% CI 0.353-0.945). CONCLUSIONS: These data support the use of XR MPH with its simplified dosing regimen for children with ADHD. Overall care costs, not solely drug acquisition costs, should be considered when assessing the value of a drug.