Background: Binge drinking among Dutch adolescents is among the highest in Europe. Few interventions so far have focused on adolescents aged 15 to 19 years. Because binge drinking increases significantly during those years, it is important to develop binge drinking prevention programs for this group. Web-based computer-tailored interventions can be an effective tool for reducing this behavior in adolescents. Embedding the computer-tailored intervention in a serious game may make it more attractive to adolescents. Objective: The aim was to assess whether a Web-based computer-tailored intervention is effective in reducing binge drinking in Dutch adolescents aged 15 to 19 years. Secondary outcomes were reduction in excessive drinking and overall consumption during the previous week. Personal characteristics associated with program adherence were also investigated. Methods: A cluster randomized controlled trial was conducted among 34 Dutch schools. Each school was randomized into either an experimental (n=1622) or a control (n=1027) condition. Baseline assessment took place in January and February 2014. At baseline, demographic variables and alcohol use were assessed. Follow-up assessment of alcohol use took place 4 months later (May and June 2014). After the baseline assessment, participants in the experimental condition started with the intervention consisting of a game about alcohol in which computer-tailored feedback regarding motivational characteristics was embedded. Participants in the control condition only received the baseline questionnaire. Both groups received the 4-month follow-up questionnaire. Effects of the intervention were assessed using logistic regression mixed models analyses for binge and excessive drinking and linear regression mixed models analyses for weekly consumption. Factors associated with intervention adherence in the experimental condition were explored by means of a linear regression model. Results: In total, 2649 adolescents participated in the baseline assessment. At follow-up, 824 ...