The objective of this study was to assess the response of anxiety and depression symptoms to methylphenidate (MPH) treatment in patients with Asperger syndrome (AS) combined with attention deficit/hyperactivity disorder (ADHD). A group of 12 patients with AS/ADHD, aged 8–18 years, received 12 weeks of MPH treatment. The severities of ADHD, anxiety, and depression symptoms were assessed by means of the ADHD Rating Scale (ADHD-RS), Screen for Child Anxiety Related Emotional Disorders, and the Children’s Depression Inventory. The severity of ADHD and depression symptoms was reduced significantly (P<0.0003 and P=0.046, respectively). No improvement in total anxiety symptoms was found, but a significant reduction was obtained in the school-related subscale of the Screen for Child Anxiety Related Emotional Disorders (P=0.0054). A positive correlation was found between the reductions in ADHD-RS and Children’s Depression Inventory scores (r=0.59, P=0.039). MPH treatment may be safe, tolerable, and effective in alleviating depression and school-related anxiety symptoms in patients with AS and ADHD.