Objective: The impact of childhood trauma was examined in 427 adolescents (54% girls, 74% Caucasian, mean = 14.6, SD = 1.5) with major depressive disorder participating in the Treatment for Adolescents with Depression Study (TADS). Method: TADS compared the efficacy of cognitive behavioral therapy (CBT), fluoxetine (FLX), their combination (COMB), and placebo (PBO). Teens were separated into four trauma history groups: (1) no trauma; (2) trauma, no abuse; (3) physical abuse; (4), and sexual abuse. The effects of treatment and trauma history on depression severity across 12 weeks of acute treatment, as measured by the Children's Depression Rating Scale-Revised (CDRS-R), were examined. Results: A significant trauma-by-treatment-by-time interaction indicated that trauma history moderated treatment. The Week 12 primary efficacy findings previously reported by TADS were replicated in the no trauma group (n = 201): COMB = FLX greater than CBT = PBO. No significant differences in treatment arms were observed among the trauma, no abuse, or physical abuse group. Teens with a history of sexual abuse treated with COMB, FLX, and PBO showed significant and equivalent improvement on the CDRS-R (mean less than 45), whereas the mean CDRS-R for the CBT group tended to remain in the depressed range (mean greater than 45). Baseline suicidality and self-reported depression were significantly related to a history of sexual abuse. Conclusions: The study was limited by the level of detail regarding childhood traumatic experiences. Results are discussed in terms of the implications for treating depressed adolescents with traumatic backgrounds. Clinical Trials Registry Information: Treatment for Adolescents with Depression Study; NCT00006286. (Contains 4 figures and 4 tables.)