Objective: To explore treatment response to Osmotic Release Oral System^® (OROS) methylphenidate in children with ADHD with and without comorbid learning disability (LD). Method: Data were analyzed from two 6-week, double-blind, randomized, placebo-controlled, crossover studies evaluating individually determined doses of OROS methylphenidate versus placebo in 135 children (ages 9 to 12 years) with ADHD with or without an LD in reading, math, or both. The sample was demographically diverse, with 31% females and more than 40% minority, predominantly African American and Hispanic. On two laboratory school days, participants received either OROS methylphenidate or placebo and were given a battery of cognitive and behavioral tests. Results: Treatment with OROS methylphenidate led to improvement in ADHD Rating Scale scores for participants with or without comorbid LD. Both groups performed better during treatment with OROS methylphenidate than placebo on measures of cognitive skills (i.e., Test of Variables of Attention, Finger Windows Backwards), academically related tasks (i.e., Dynamic Indicators of Basic Early Literacy Skills, Test of Handwriting Skills–Revised, Permanent Product Math Test), and observed classroom behavior (i.e., Swanson, Kotkin, Alger, M-Flynn, and Pelham Scale). Conclusion: In children with ADHD with or without comorbid LD, behavior and performance improved during treatment with OROS methylphenidate. (J. of Att. Dis. 2012; XX(X) 1-XX)