Objective: Oppositional defiant disorder (ODD) is the most common comorbid condition in childhood ADHD. This trial was prospectively designed to explore ODD symptoms in ADHD adults. Method: A total of 86 patients in this placebo-controlled, double-blind trial of methylphenidate transdermal system (MTS) were categorized based on the presence of ODD symptoms in childhood and adulthood, and then were compared for baseline and outcome differences. Results: In all, 42% met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ODD as adults and were significantly more impaired on measures of ADHD, personality disorder, and substance abuse and 27% had childhood ODD that had resolved. Childhood and adult ODD symptoms were significantly correlated. ODD and ADHD symptoms improved significantly with MTS (p < .001), and the most consistently significant results were found in participants with adult ODD. Conclusion: A total of 69% met criteria for ODD as children and/or adults. Understanding how ODD interacts with ADHD to impact personality disorder, substance abuse, and treatment response has important clinical, social, and theoretical implications. (J. of Att. Dis. 2011; XX(X) 1-XX)