Purpose: Few dating violence prevention programs assess how variations in initial violence risk affects responsiveness. This study examines the efficacy of Date SMART, a dating violence and sexual risk prevention program designed to target high-risk adolescent girls, in preventing dating violence in the context of varying initial levels of depressive symptoms. Method: A diverse sample of N = 109 female adolescents with a history of physical dating violence participated in a randomized controlled trial of the Date SMART program and a knowledge only (KO) comparison. Results: Using baseline depression level as a primary risk factor, a series of multilevel models revealed significant main effects of baseline depression such that higher baseline depression was associated with greater physical dating violence perpetration and victimization. Results also showed a three-way interaction for assessment point, depressive symptoms, and condition for physical dating violence perpetration. Specifically, those with higher baseline depression in Date SMART showed significantly less physical dating violence perpetration at follow-ups compared with those with higher baseline depression in the KO group. This difference in violence reduction between conditions was not observed for those with lower baseline depression. Discussion: Date SMART appears to effectively reduce physical dating violence perpetration in those with higher levels of initial risk. Current findings support that adolescents with different risk profiles respond differently to violence prevention programs.