Anxiety and depression are disorders associated with both high prevalence rates and comorbidity in adolescence. Despite the fact that schools are a key resource for mental health promotion, programs for the prevention of mental disorders are scarce in this context. The present work aims to study the efficacy of a program based on transdiagnostic cognitive-behavioral therapy to jointly prevent anxiety and depression. Specifically, the efficacy of this program is studied in relation to variables related to the school context and wellbeing: school adjustment, indiscipline in the classroom, problems with peers, satisfaction with life, quality of life and self-esteem. A total of 151 adolescents were randomized to the experimental group or the control group and completed a range of self-report questionnaires at three intervals (including a three-month follow-up). The intervention consisted of nine weekly sessions administered during school hours by two psychologists. The results show a reduction in the academic expectations in the control group, while these remain constant in the experimental group. The implications of the results of this study are discussed in relation to previous literature and the limitations of this trial.