BACKGROUND: Depression is a common and disabling condition. In Chile, assistance is guaranteed by law through a national program for depression in primary care services, and there is evidence of effective treatment for depressed women. However, there is a shortage of evidence-based treatments for depression in adolescents. The incorporation of technology to expand therapeutic options is becoming more common. This proposal aims to compare the efficacy of therapy that enhances traditional face-to-face cognitive-behavioral therapy (CBT) with a computer-based program versus usual care to treat depression in adolescents in primary care clinics in Santiago, Chile. METHODS AND DESIGN: This is a two-arm, single-blind, randomized controlled trial with a target enrollment of 216 depressed adolescents between 15 and 19 years of age, attending four primary care clinics in Santiago, Chile. In the active arm, depressed adolescents will receive eight sessions of computer-assisted CBT, led by trained psychologists on a weekly basis. In the control arm, depressed adolescents will receive treatment as usual from the primary care centers. Mean depression scores and indicators of dysfunctional thoughts, problem-solving strategies, and health-related quality of life will be measured at baseline and four and six months after randomization. DISCUSSION: As far as we know, this is the first randomized controlled trial of a computer-assisted CBT intervention for depressed adolescents in a Latin American country. TRIAL REGISTRATION: Clinical Trials: NCT01862913.