Inconsistent methylphenidate (MPH) dose-response relationships are often observed in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study examined whether informant-reported behavioural criteria or “cool” executive/working memory (EWM) and “hot” self-regulation (SR) neuropsychological factors differentiated MPH responders from non-responders. Fifty-six children with physician-diagnosed ADHD underwent four-week randomized, double-blind, placebo-controlled MPH trials. Children were administered a battery of neuropsychological measures sensitive to ADHD to evaluate cognitive MPH response. Classroom observations and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) parent/teacher reports were used to evaluate behavioural MPH response. EWM/SR factor scores discriminated cognitive MPH responders from non-responders, as did DSM-IV-TR Hyperactive-Impulsive criteria. Univariate F tests and Wilks ƛ results for EWM, SR, and DSM-IV-TR Hyperactive-Impulsive measures suggest their potential utility in detecting MPH response, whereas DSM-IV-TR Inattentive criteria were less useful. Results suggest practitioners should consider neuropsychological test performance in conjunction with behavioural report of ADHD symptoms when considering MPH treatment response.