Evidence suggests that parental marital discord contributes to the development of internalizing and externalizing symptoms in children and adolescents. Few studies, however, have examined the association between parental marital discord and youth's response to treatment. The present study examined the impact of interparental discord on treatment response in a randomized control trial of adolescents with major depression enrolled in the Treatment for Adolescents with Depression Study (TADS). Participants were 260 adolescents from two-parent households randomly assigned to one of four treatment groups: fluoxetine (FLX), cognitive behavior therapy (CBT), their combination (COMB), or placebo (PBO). Logistic regressions revealed that parental marital discord interacted with youth gender and co-morbid oppositionality symptoms to predict group differences in treatment response.