OBJECTIVES: To estimate the cost-effectiveness of the single-dose extended release Methylphenidate vs the multi-dose immediate release Methylphenidate and single-dose Atomoxetine for the management of ADDH in Mexico. METHODS: A cost-effectiveness analysis was developed, under a decision model. The cost-effectiveness ratio was estimated for extended release methylphenidate compared to other drug alternatives. A retrospective analysis was made of all patients seen at the IMSS (Mexican Institute of Social Security) during 2004, with diagnosed ADDH. Patient cohorts were derived from IMSS data base, and they were used as an analysis pattern for each therapeutic alternative. In order to determine the effectiveness rates for each drug, and to obtain the “clinical outcomes”, a meta-analysis of national and international literature was made. To compare the effectiveness, the ADHR-RS/Total, ADHD-RS/Hyperactivity, ADHD-RS/Attention, CPRS-R Inattention/Overactivity and CPRS-R/Opposition-Challenge scales were used. A comparison was also made of all reported adverse events. A decision tree was utilized, based on its care, and the costs were determined for each node. Costs for drug therapy, specialty ambulatory consultations in pediatrics, neurology, and psychology, hospitalization, time spent in hospitals, laboratory and office tests, and labor productivity were considered. RESULTS: The extended release methylphenidate OROS attained the most significant results regarding healthcare measures. As for the ADHD-RS Total score, it showed a difference in improvement of almost 34%, compared to Methylphenidate IR, and almost 59% compared to Atomoxetine. The extended release methylphenidate OROS (CONCERTA®) leads to savings of $3213 for hospitalization days avoided, and it is the most cost-effective and cost-saving strategy, compared to Methylphenidate IR and Atomoxetine. CONCLUSION: Extended release methylphenidate OROS is an efficient, cost-effective, and cost-saving alternative compared to Methylphenidate IR and Atomoxetine.