Objective: Delayed-release and extended-release methylphenidate (DR/ER-MPH), the first stimulant predicted to be absorbed primarily in the colon, demonstrated significant improvements in attentiondeficit/hyperactivity disorder (ADHD) symptoms and functional impairment from awakening until evening versus placebo in clinical trials. The clinical significance of these improvements was explored post hoc by examining response and remission thresholds as well as safety in the context of dose optimization. Methods: Data from the open-label, treatment-optimization phase of a phase 3 study of DR/ER-MPH in children (aged 6-12 years) with ADHD, as diagnosed by DSM-5 criteria and enrolled between July 2015 and March 2016, were analyzed. Thresholds for response (anchored to Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and remission were applied to ADHD Rating Scale-IV (ADHD-RS-IV), Before School Functioning Questionnaire (BSFQ), and Parent Rating of Evening and Morning Behavior, Revised, Morning Subscale (PREMB-R AM) and Evening Subscale (PREMB-R PM) scores. Rates of response, remission, and treatment-emergent adverse events by starting dose were examined. Results: Mean DR/ER-MPH dose increased from 29.7 mg/d at baseline (51% on 20 mg/d; 49% on 40 mg/d) to 66.2 mg/d at week 6. At week 6, most participants achieved response/remission thresholds