This is the final version of the article. Available from the publisher via the DOI in this record. ; BACKGROUND: Depression in adolescents is a significant problem that impairs everyday functioning and increases the risk of severe mental health disorders in adulthood. Relatively few adolescents with depression are identified and referred for treatment indicating the need to investigate alternative preventive approaches. STUDY DESIGN: A pragmatic cluster randomised controlled trial evaluating the effectiveness of a school based prevention programme on symptoms of depression in "high risk" adolescents (aged 12-16). The unit of allocation is year groups (n = 28) which are assigned to one of three conditions: an active intervention based upon cognitive behaviour therapy, attention control or treatment as usual. Assessments will be undertaken at screening, baseline, 6 months and 12 months. The primary outcome measure is change on the Short Mood and Feeling Questionnaire at 12 months. Secondary outcome measures will assess changes in negative thoughts, self esteem, anxiety, school connectedness, peer attachment, alcohol and substance misuse, bullying and self harm. DISCUSSION: As of August 2010, all 28 year groups (n = 5023) had been recruited and the assigned interventions delivered. Final 12 month assessments are scheduled to be completed by March 2011. TRIAL REGISTRATION: ISRCTN19083628. ; This project is funded by the NIHR Health Technology Assessment programme (project number 06/37/04).