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Abstract The conceptualization and empirical knowledge base related to major depression has increased dramatically in recent years. We now have well-developed and validated models of depression from a range of theoretical perspectives. These models have significantly enhanced the development of effective treatments and preventative interventions. Although various prevention programs are available, Web-based protocols can enhance accessibility to evidence-based prevention programs. The current study involved a randomized controlled trial focused on the prevention and treatment of depression in high-risk first- and second-year undergraduate students. Three Internet-delivered preventative programs were compared: cognitive behavioral therapy (CBT; MoodGym), attentional bias modification, and an active attentional control condition. Participants (n ¼ 350) completed symptom measurement pre- and post-intervention (6 weeks) and again at a 4-month follow-up, when they were also administered a structured diagnostic interview. Participants in the CBT condition showed more dramatic and continuous depressive symptom improvement between baseline and follow-up than did participants in the other two conditions. In addition, significantly fewer individuals in CBT condition met diagnostic criteria for major depression at follow-up than in the other conditions. These findings have important implications for future early intervention research and practice.