Objectives: In this study the efficacy of buspirone was compared with methylphenidate in children and adolescent with attention deficit-hyperactivity disorder (ADHD). Methods: In this randomized double blind clinical trial with crossover design, 40 children and adolescents (6-16 years old) with the diagnosis of ADHD were studied. The samples were selected by conventional method and categorized by blocked randomization into buspirone and methylphenidate groups. This study has two 8-week phases with one week wash-out period. Both medications were prescribed with the dose of 0.5 mg/kg/day. Effectiveness was evaluated using teacher and parents forms of ADHD Rating Scale (ADHD-RS) for both groups. Questionnaires were completed in baseline and every two weeks during the eight-week phase. Medication side effect profile was evaluated. Data were analyzed by repeated measurement ANOVA. Results: At the end of each phase, the scores of attention deficit, hyperactivity and impulsivity had significant decrease in comparison with baseline and previous weeks of study for both drugs and no significant difference was detected between groups. The positive effect of methylphenidate in decreasing the symptoms was detected earlier than buspirone. Conclusion: Buspirone seems to be as effective as methylphenidate in treating ADHD with less side effects.