Objective: The aim of this study is to investigate the methylphenidate (MPH) treatment response in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) with and without epilepsy. Methods: Ninety-four children and adolescents with ADHD consisting of 47 with and 47 without epilepsy were enrolled into the study. The patients were evaluated by DSM-IV-TR, the Stroop test, the Conners' Parent and Teacher Rating Scales. The groups were matched with regard to age, gender, ADHD subtype and comorbidity. The Stroop test was performed three times: during baseline (S-1); at the third month of the MPH treatment (S-2); after drug holiday of the treatment with MPH which lasted for six months (S-3). Stroop total time (ST) and Stroop total error+correction (SEC) scores were analyzed. Results: The mean ST-3 and SEC-3 scores were significantly higher in cases with ADHD-attention deficit (ADHD-AD) subtype with the epilepsy group compared to ADHD-combined type (ADHD-CT) in the epilepsy group, whereas there was no significant difference detected in the non-epilepsy groups. While in the boys with/without epilepsy and the girls without epilepsy and were demonstrated significant reductions in all recorded ST and SEC scores during/after treatment in comparison with the initial scores, a similar relationship could not be shown for the girls with epilepsy. Conclusion: It is noted that gender and the ADHD subtypes may affect drug choice in patient with ADHD cases comorbid with epilepsy. One of the noticeable results of our study is was that the Stroop scores is no significant change with methylphenidate treatment in especially in girls with ADHD and epilepsy.