OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder of childhood, and the methylphenidate hydrochloride (MPH) is the most frequently and well-established prescribed pharmacotherapy for ADHD.  Warnings by the United States Food and Drug Administration on psychiatric adverse effects have concerns for drug safety.  Existing studies to date demonstrate that MPH’s safety of children with ADHD which get inconsistent results.  The purpose was to evaluate the potential association between MPH treatment and the subsequent development of psychiatric disorders such as disruptive, anxiety, mood, learning, tic and substance-related disorders. METHODS: A retrospective cohort study was conducted.  Study subjects selected were aged 6 to 18 years on the date of the first diagnosed for ADHD between 2001 and 2006.  Patients were divided into 2 groups: ever-using MPH and not-using MPH.  The authors conducted case-control matching on the propensity score to reduce selection bias.  The Cox Proportional Hazards Model was used to assess the association of use of MPH with the subsequent risks of psychiatric events occurring. RESULTS: The results shows that the MPH group had a significantly higher hazard ratio (HR) of patients diagnosed with oppositional defiant disorder (ODD) (HR = 1.807, P <0.001), conduct disorder (CD) (HR = 1.225, P = 0.0460), and anxiety disorders (AD) (HR = 1.921, P <0.001).  The MPH group had a significantly lower HR of patients diagnosed with learning disorders (LD) (HR = 0.818, P = 0.0029).  In addition, the authors found the MPH group had a significantly higher HRs of ODD and CD and a significantly lower HR of LD in boys only. CONCLUSIONS: Our study found that MPH treatment is associated with a higher risk of development of oppositional defiant disorder, conduct disorder and anxiety disorders and a lower risk of learning disorders.