The aim of this study was to compare the safety, efficacy, tolerability, and the effects of atomoxetine and OROS-MPH on executive functions in children with ADHD. This study was an open-label study that only included two medication groups. Children were randomized to open-label atomoxetine or OROS-MPH for 12 weeks. Primary efficacy measures were T-DSM-IV-S, CGI-I and neuropsychological tests battery. Safety assessments included electrocardiogram, adverse events checklist and laboratory tests. According to the endpoint improvement scores of CGI and parents T-DSM-IV-S, treatment responses were not significantly different between the two study groups. OROS-MPH led to a significantly greater reduction in teacher T-DSM-IV-S scale scores. OROS-MPH was more effective than atomoxetine on Stroop-5 time and number of corrections. Significant decrease in the percentage of perseverative errors on WCST in the OROS-MPH group was seen (p = 0.005). The most frequently reported adverse events in the atomoxetine group were anorexia, nausea, nervousness, weight loss, abdominal pain, and somnolence. In the OROS-MPH group, patients most frequently reported anorexia, nervousness, insomnia, headache, nausea, and weight loss. When all these results are considered, although both drugs can be considered effective in ADHD treatment, more remarkable improvement is provided by OROS-MPH based on the rates across informant (i.e., teachers, clinicians) and neuropsychological evaluation.