This study examined the efficacy and safety of osmotic release oral system methylphenidate (OROS MPH) as compared with immediate-release MPH (IR MPH) in children with attention-deficit/hyperactivity disorder (ADHD) in Taiwan. Sixty-four children with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) ADHD, ages 6–15 years, were randomized to OROS MPH once daily (n = 32) and IR MPH three times daily (n = 32) in an open, randomized, active-controlled equivalent 28-day trial. The main outcome measures included the Conner's Teacher Rating Scale -Revised: Short Form and Conner's Parent Rating Scale-Revised: Short Form, and other measures of social adjustment and side effects. Results showed significant reductions in the core ADHD symptoms, which did not differ between the two treatment groups. Compared to the IR MPH group, the OROS MPH group showed a significantly greater slope of reductions in ADHD symptoms and decline in the severity of problems at school, and with peers and parents over time. There was no difference in rates of side effect profile between the two groups. Our findings suggest that OROS MPH is superior over IR MPH in the greater magnitude of improvement over study period without increased side effects in the Chinese population.