OBJECTIVES: To evaluate the cost-effectiveness of frequently used long acting treatments for children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in the U.S. Military Health System (MHS). METHODS: A decision analytic model compared the cost-effectiveness of three commonly used long acting treatments for ADHD in the MHS (methylphenidate OROS, mixed amphetamine salts extended-release, and atomoxetine) to treatment with methylphenidate immediate-release (MPH IR) over a one year time horizon. Inputs for model parameters were derived from published literature. Treatment efficacy was estimated from a mixed treatment comparison model of published randomized controlled trials with response to treatment defined as either very much improved or much improved on the physician-rated Clinical Global Impression of Improvement scale. Health care costs were measured from a MHS perspective in dollars and drug costs were based on Federal Supply Schedule prices. Treatment outcomes were measured in quality-adjusted life-years (QALYs). The model considered two scenarios. One of equal patient preference for response to treatment and another that assumed a greater preference for response with extended-release and non-stimulant products compared to MPH IR. Model uncertainty was evaluated with probabilistic sensitivity analyses and cost-effectiveness acceptability curves. RESULTS: Under a scenario of equal patient preferences, methylphenidate OROS was slightly more effective than MPH IR with an estimated incremental cost-effectiveness ratio (ICER) of $111,536/QALY. Greater patient preference for extended-release and non-stimulant products increased the estimated benefit of the long acting treatments. This improvement lowered the ICER for methylphenidate OROS to $27,214/QALY compared to MPH IR. Atomoxetine was also on the cost-effectiveness frontier at an additional cost of $34,239/QALY compared to treatment with methylphenidate OROS. Under both scenarios, mixed amphetamine salts extended-release was dominated by methylphenidate OROS. CONCLUSION: Long acting treatments for ADHD in the MHS were cost-effective at commonly accepted thresholds only under a scenario that assumed greater patient preference for response to these products.