Aims: To evaluate the effectiveness and cost-effectiveness of alcohol screening and brief intervention for adolescents delivered within the school setting. Method: Multi-centre, pragmatic, prospective randomised controlled trial conducted across different regions of England. We evaluated the effectiveness and cost-effectiveness of an Alcohol Screening and Brief Intervention (ASBI) in addition to Personal Health and Social Education (PHSE) compared to PHSE alone for adolescents aged 15 years in school. Our primary outcome was quantity of alcohol consumed at 12-months, assessed in units of alcohol. We also assessed alcohol-related problems, drinking motives and health and wellbeing. The trial was registered with current controlled trials (ISRCTN45691494). Results: While 60% of the study population had reduced their alcohol consumption at month 12, we found no difference in effectiveness between ASBI and PHSE for any of our outcome measures. The ASBI was not found to be cost-effective compared to PHSE. Conclusions: The results of the study suggest that it is not worthwhile implementing ASBI in a school setting. This concurs with other recent evidence of the effectiveness of ASBI for adolescent populations.