This study evaluated the efficacy of 2 programs for preventing depressive symptoms in adolescents. Participants were 380 high school students randomly assigned to a cognitive-behavioral program (CB), an interpersonal psychotherapy-adolescent skills training program (IPT-AST), or a no-intervention control. The interventions involved eight 90-min weekly sessions run in small groups during wellness classes. At postintervention, students in both the CB and IPT-AST groups reported significantly lower levels of depressive symptoms than did those in the no-intervention group, controlling for baseline depression scores; the 2 intervention groups did not differ significantly from each other. The effect sizes, using Cohen's d, for the CB intervention and the IPT-AST intervention were 0.37 and 0.26, respectively. Differences between control and intervention groups were largest for adolescents with high levels of depressive symptoms at baseline. For a high-risk subgroup, defined as having scored in the top 25th percentile on the baseline depression measure, the effect sizes for the CB and the IPT-AST interventions were 0.89 and 0.84, respectively. For the whole sample, sociotropy and achievement orientation moderated the effect of the interventions. Intervention effects were short term and were not maintained at 6-month follow-up.