Objective: This trial evaluated the effect of methylphenidate transdermal system (MTS) on the full spectrum of adult symptoms (attention-disorganization, hyperactivity-impulsivity, emotional dysregulation [ED], and oppositional-defiant disorder [ODD]) found in this disorder. Method: This placebo-controlled, double-blind, flexible-dose, crossover trial employed the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) and Connor's Adult ADHD Rating Scale (CAARS) and two measures of adult ODD. Treatment responses of all participants and four subgroups (ADHD-alone, ADHD + ED, ADHD + ODD, and ADHD + ED + ODD) were assessed. Results: Around 23% of baseline participants were ADHD alone, 31% were ADHD + ED, 10% were ADHD + ODD, and 36% were ADHD + ED + ODD. There was a significant treatment effect for all symptom areas and all four subgroups. MTS was associated with significantly more adverse events, especially dermatologic side effects. Conclusions: MTS was effective in treating adult ADHD. This clinical trial included numerous participants meeting criteria for ED and ODD. All ADHD symptoms responded positively to treatment with MTS. (Contains 3 tables.)