OBJECTIVES: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurobehavioral disorder and one of the most prevalent chronic health problems affecting school-age children, representing a costly major public health problem. Keeping in view, the substantial economic burden, the objective of this study was to conduct a cost-minimization analysis of once-a-day extended-release (ER) versus two-times-daily immediate-release (IR) methylphenidate for the treatment of ADHD patients. METHODS: Major literature databases were systematically searched to identify appropriate randomized clinical trials and meta-analyses to obtain costs associated with both the alternative formulations from a payers (third party) perspective.  Medical costs included cost of drug, cost of assessments, cost of non-compliance, cost of injuries/accidents and cost of in-school administration and were obtained from published literature. All costs were adjusted to 2012 USD using consumer price index. The expected outcome was considered to be the same for both the formulations and a cost minimization analysis was performed using a decision tree approach. Multiple one-way sensitivity analyses were performed on all cost variables  to evaluate the robustness of the results. RESULTS: The ER regimen of methylphenidate resulted in a total annual cost of $4685 per patient which was less costly as compared to the IR regimen that resulted in a total annual cost of $9524 per patient for the treatment of ADHD. One-way sensitivity analyses results were consistent. CONCLUSIONS: In our study Methylphenidate ER had 50.81% less annual economic burden as  compared to the IR regimen for the treatment of ADHD patients.