Background: Medication treatment studies of ADHD have typically not assessed effects on reading performance, although reading difficulties frequently co-occur in children with ADHD. The current study characterizes the effects of lisdexamfetamine dimesylate (LDX; Vyvanse[R], Shire US Inc.), at peak efficacy, on reading performance in children with ADHD. Method: Children (ages 6-12; N = 26) with ADHD enrolled in a modified laboratory school study with an open-label, dose-optimization phase of LDX (30-70 mg/d). The Gray Oral Reading Test-4 (GORT-4) with measures of rate, accuracy, and comprehension was administered at baseline and 3-4 hr postdose, following 4 to 5 weeks of optimal dose titration. Results: Treatment reduced ADHD symptoms. Reading rate was improved, especially among children with higher verbal fluid reasoning without additional symptoms of neurodevelopmental delay. No differences were observed for reading accuracy or comprehension. Conclusion: Endophenotypical profiles may predict drug effects in specific skill areas, such as reading rate. (Contains 3 figures and 5 tables.)