Aim: To psychometrically assess cognitive domains in adolescents with ADHD during long-term open treatment with robust dosing of extended-release methylphenidate (OROS MPH).Methods: Data were derived from a prospective clinical study of adolescent ADHD, employing the Cambridge Neuropsychological Test Automated Battery (CANTAB), before and after up to one year of treatment with OROS MPH. In the absence of placebo control, a similar age and gender group of youth without ADHD served as comparators.Results: During the course of treatment with OROS MPH, ADHD youths performance significantly improved across multiple CANTAB tasks, including spatial working memory, rapid visual processing, verbal recognition memory, set shifting, and inhibition/vigilance. ADHD subjects scores in several CANTAB tasks, including spatial working memory, planning, and set shifting, were significantly more impaired at baseline compared to the non-ADHD comparison group; these significant differences were no longer seen at endpoint.Conclusions: Statistically significant improvements in multiple cognitive domains were observed in a sample of adolescents with ADHD over the course of 12 months of robust treatment with extended-release methylphenidate. Rigorous, monitored stimulant treatment may be associated with objectively determined cognitive benefits; however, practice effects in this open trial cannot be ruled out. Further study on this important topic is warranted.