Objective: To test whether an optimal dose of Quillivant XR (methylphenidate extended-release oral suspension [MEROS]) would significantly reduce symptoms of ADHD in children. Method: A randomized, double-blind, placebo-controlled, cross-over, efficacy, safety, and tolerability study of MEROS in 45 children aged 6 to 12 years (open-label dose-optimization phase, followed by double-blind cross-over period). Results: MEROS was significantly more efficacious than placebo during double-blind cross-over laboratory classroom days (Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale and Permanent Product Measure of Performance). During the open-label phase, improvements were observed in scores of ADHD Rating Scale-IV, and Clinical Global Impression-Severity and -Improvement Scales. No occurrences of suicidal ideation or behavior were recorded; the most common open-label treatment-emergent adverse events were typical of stimulant use: decreased appetite, insomnia, and abdominal pain. Conclusion: MEROS was efficacious in the treatment of children aged 6 to 12 years with ADHD, with a safety profile similar to that of other extended-release methylphenidate pharmacotherapies.