Background: Oppositional defiant disorder (ODD) is a leading cause of referral for youth mental health services; yet, many uncertainties exist about ODD given it is rarely examined as a distinct psychiatric disorder. We examined the lifetime prevalence, onset, persistence, and correlates of ODD. Methods: Lifetime prevalence of ODD and 18 other DSM-IV disorders was assessed in a nationally representative sample of adult respondents (n = 3,199) in the National Comorbidity Survey Replication. Retrospective age-of-onset reports were used to test temporal priorities with comorbid disorders. Results: Lifetime prevalence of ODD is estimated to be 10.2% (males = 11.2%; females = 9.2%). Of those with lifetime ODD, 92.4% meet criteria for at least one other lifetime DSM-IV disorder, including: mood (45.8%), anxiety (62.3%), impulse-control (68.2%), and substance use (47.2%) disorders. ODD is temporally primary in the vast majority of cases for most comorbid disorders. Both active and remitted ODD significantly predict subsequent onset of secondary disorders even after controlling for comorbid conduct disorder (CD). Early onset (before age 8) and comorbidity predict slow speed of recovery of ODD. Conclusions: ODD is a common child- and adolescent-onset disorder associated with substantial risk of secondary mood, anxiety, impulse-control, and substance use disorders. These results support the study of ODD as a distinct disorder. Prospective and experimental studies are needed to further delineate the temporal and causal relations between ODD and related disorders.