Objective: To examine efficacy and safety of adjunctive guanfacine extended release (GXR) on morning and evening ADHD symptoms using the Conners’ Global Index–Parent (CGI-P) and Before-School Functioning Questionnaire (BSFQ). Method: Participants 6 to 17 years with ADHD (N = 461) and suboptimal psychostimulant response were maintained on current psychostimulants and randomized to dose-optimized GXR (≤4 mg/d) in the morning (GXR AM) or evening (GXR PM), or placebo. Results: CGI-P scores improved with GXR (morning assessment, GXR AM, placebo-adjusted least squares [LS] mean = –1.7, GXR PM = –2.6; evening assessment, GXR AM = –2.4, GXR PM = –3.0; all ps < .01). Parent-rated BSFQ scores reflected improved morning functioning with GXR (GXR AM, placebo-adjusted LS mean = –5.1; GXR PM = –4.7; both ps < .01). Most adverse events were mild or moderate. Conclusion: Adjunctive GXR AM or GXR PM was associated with improvements in morning and evening ADHD symptoms in children and adolescents. (J. of Att. Dis. 2013; XX(X) 1-XX)