This study aimed to compare the effects of osmotic release oral system-methylphenidate (OROS-MPH) and atomoxetine (ATX) on executive function in children and adolescents with attention deficit hyperactivity disorder (ADHD) by a randomized controlled trial. Subjects who met DSM-IV ADHD criteria were randomized to receive either OROS-MPH or ATX treatment. The doses were titrated to achieve optimal response and then maintained for 4–6 wk. A battery of executive function tests and the Behavior Rating Inventory of Executive Function (BRIEF) were administered to subjects who completed the dose titration (OROS-MPH, n=85; ATX, n=57) at the pre- and post-treatment periods. Forty-six children without ADHD were recruited as controls. Both OROS-MPH and ATX significantly improved scores in the Rey Complex Figure Test (RCFT), digit span, and Stroop color-word task. The scores in RCFT and the reverse digit span were not significantly different from the control group at post-treatment assessment (OROS-MPH=ATX=control, p>0.05), whereas the word interference time of the Stroop test was still more than that of the control group (OROS-MPH=ATX>control, p>0.05). OROS-MPH also significantly improved the total correct response in the verbal fluency test to normal level, and the shifting time in the trail-making test to subnormal level. The current findings suggest both OROS-MPH and ATX improved executive function generally in children and adolescents with ADHD, and could return working memory back to normative performance level.