Our objective was to conduct the first randomized controlled trial of the efficacy of a group mindfulness program aimed at reducing and preventing depression in an adolescent school-based population. For each of 12 pairs of parallel classes with students (age range 13–20) from five schools (N = 408), one class was randomly assigned to the mindfulness condition and one class to the control condition. Students in the mindfulness group completed depression assessments (the Depression Anxiety Stress Scales) prior to and immediately following the intervention and 6 months after the intervention. Control students completed the questionnaire at the same times as those in the mindfulness group. Hierarchical linear modeling showed that the mindfulness intervention showed significantly greater reductions (and greater clinically significant change) in depression compared with the control group at the 6-month follow-up. Cohen's d was medium sized (>.30) for both the pre-to-post and pre-to-follow-up effect for depressive symptoms in the mindfulness condition. The findings suggest that school-based mindfulness programs can help to reduce and prevent depression in adolescents.