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Objective: To assess the global functioning and clinical outcomes of children and adolescents with bipolar disorder, children and adolescents with bipolar disorder and substance use disorder (SUD) comorbidity and healthy controls., Methods: This study had a cross-sectional design. Participants were children and adolescents aged between 6 and 17 years, and data were collected between 2003 and 2015. Psychiatric diagnosis was established according to DSM-IV criteria using the Kiddie-SADS-Present and Lifetime Version or the Mini-International Neuropsychiatric Interview for Children and Adolescents. Global functioning was assessed using the Children's Global Assessment Scale. Depressive symptoms were assessed using the Children's Depression Rating Scale. Manic symptoms were measured using the Young Mania Rating Scale, and the severity of anxious symptoms was assessed using the Screen for Child Anxiety Related Disorders., Results: The sample included 187 children and adolescents with bipolar disorder, 29 with BD and SUD comorbidity, and 115 healthy controls. Children and adolescents with BD and SUD comorbidity presented later onset of mood disorder (P < .001); higher rates of lifetime history of suicide attempt (P < .001), lifetime history of psychosis (trend toward significance: P = .076), and lifetime hospitalization (P < .001); and higher severity of depressive symptoms (trend toward significance: P = .080) as compared to those with BD without SUD comorbidity. In addition, both diagnosis groups presented higher rates of functional impairment when compared to controls (P < .001). Moreover, BD and SUD comorbidity presented higher functional impairment, as compared to BD without SUD comorbidity (P = .020)., Conclusions: Children and adolescents with bipolar disorder and substance use disorder comorbidity present a worse clinical course than those with bipolar disorder but without substance use disorder comorbidity., (© Copyright 2017 Physicians Postgraduate Press, Inc.)