White matter (WM) integrity is an important factor for the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) in adolescents. In this study, we hypothesized that adolescents with attention deficit hyperactivity disorder with comorbid bipolar disorder (ADHD+BD) would yield different pattern and extent of WM abnormalities than ADHD and BD. Sixty adolescents were categorized into four groups as ADHD, BD, ADHD+BD and healthy controls. The comparative diffusion tensor imaging analyses were performed between each patient group and healthy controls. Adolescents with ADHD+BD displayed different pattern and extent of WM abnormalities than ADHD and BD revealed by tract-based spatial statistics.