Comorbidity and complexity of cases seen in clinical work form a basis for discounting the applicability and generality of evidence-based treatments (EBTs). The authors evaluated treatment outcomes in 2 samples of clinically referred children who met criteria for oppositional defiant disorder (n = 183; 42 girls, 141 boys; ages 3-14) or conduct disorder (n = 132; 35 girls, 97 boys; ages 7-14) but varied in comorbidity (up to 5 additional disorders). In addition to comorbidity, 4 domains of case complexity were evaluated: scope and severity of child dysfunction, socioeconomic disadvantage, parent and family functioning, and barriers that emerged during treatment. Comorbidity was associated with greater therapeutic change. Children who varied in comorbidity did not differ on outcome measures at the end of treatment. Complexity was either unrelated or positively related to therapeutic change. As an exception, perceived barriers were associated with less child improvement, but, even with high barriers, effect sizes for these children were large. The findings suggest that comorbidity or complexity of cases does not necessarily influence outcome or limit the applicability of EBTs.