The current study was designed to investigate the changes that occur in depression, anxiety, obsessive-compulsive symptoms and health-related quality of life during methylphenidate (MPH) treatment in children with attention-deficit hyperactivity disorder (ADHD). Forty-five treatment naive children with ADHD, aged 8-14, were assessed based on self, parent and teacher reports at the baseline and at the end of the first and third month of MPH treatment regarding changes in inattention, hyperactivity, impulsivity, depression, anxiety and obsessive-compulsive symptoms. Changes in the quality of life were also noted. Repeated measures of analysis of variance (ANOVA) tests with Bonferroni corrections were conducted in order to evaluate the data. Symptoms of inattention, hyperactivity and impulsivity were significantly reduced (p < 0.017) following a three-month MPH treatment. There were significant decreases in depression (p = 0.004), trait anxiety (p = 0.000) and checking compulsion symptom scores (p = 0.001). Moreover, parents reported significant improvements in psychosocial (p = 0.001) and total scores (p = 0.009) of quality of life, despite no change in physical health scores (p > 0.05). Children's ratings of quality of life measures showed no significant changes in physical health and psychosocial scores (p > 0.05), while total scores significantly improved (p = 0.001) after the treatment. Over a three-month MPH treatment, depression, trait anxiety and checking compulsion symptoms decreased and quality of life seemed to improve along with those of inattention, hyperactivity and impulsivity.