OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a common mental illness of childhood, and the methylphenidate (MPH) is the most use and effective drugs in treating ADHD.  Some recent studies found long-term use of MPH could cause side effects (SE) such as cardiovascular disease, mental illness, and substance abuse.  This study focused on the pharmacological treatment of ADHD using MPH, and to evaluate the relationship between MPH and potential SE specifically on above three diseases. METHODS: The data source was the overall ADHD patients’ cohort during 2000~2007 from a population-based dataset, the National Health Insurance Research Database, in Taiwan. Children (aged 6-18) having newly diagnosed ADHD was included from claims data between January 1, 2001 and December 31, 2006.  Newly diagnosed patient was identified as no diagnosed record before 12 months since initial ADHD diagnosed and data on SE were collected during the 12 months after each patient’s initial ADHD diagnosed.  These patients were divided into two groups according to whether they were using MPH or not. RESULTS: We captured 61,878 new diagnosed cases (27,656 cases in MPH group, 34,222 in non-MPH group) during the study period.  The Cox proportional hazards model analysis demonstrated that the MPH group have no significant higher hazard ratio (HR) of diagnose for cardiovascular disease and substance abuse.  However, the MPH group have significant higher HR of diagnose for mental illness such as oppositional defiant disorder (HR=1.737, 95% CL: 1.333-2.264) and anxiety disorders (HR=2.858, 95% CL: 2.517-3.244). CONCLUSIONS: Taking methylphenidate to treat ADHD did not increase HR of cardiovascular disease and substance abuse, but may have potential side effect of some mental illness such as oppositional defiant disorder and anxiety disorders.