Abstract Background A growing body of literature indicates that adolescent girls who talk with close friends about interpersonal problems or worries in an excessive, speculative way, and with an intense focus on distress (i.e., co-rumination ) are at heightened risk for developing internalizing symptoms and disorders as well as reduced friendship quality. However, to date, there are no prevention programs available that target high levels of co-rumination between adolescent girls. As such, we developed the blended school-based mindfulness prevention program Happy Friends, Positive Minds (HFPM) that targets co-rumination at the dyadic level, i.e., between two close female friends. The aim of this trial is to evaluate the effectiveness of HFPM to reduce co-rumination and internalizing problems and to enhance wellbeing and social-emotional behavior in Dutch adolescent girls. Methods A cluster Randomized Controlled Trial (cRCT) will be conducted to evaluate HFPM effectiveness. We will recruit 160 female friendship dyads ( n = 320 girls) aged 13 to 15 years who will be characterized by high levels of self-reported co-rumination. The cRCT has two arms: (1) an intervention condition in which 160 girls (80 friendship dyads) will receive the 14-week HFPM program in two consecutive cohorts (cohort 1 in academic year 2023/2024 and cohort 2 in academic year 2024/2025, and (2) a control condition in which 160 girls (80 dyads) will receive care-as-usual (CAU) in two consecutive cohorts (cohort 1 in academic year 2023/2024 and cohort 2 in academic year 2024/2025). Data will be collected at baseline (T0), during the program (T1;T2; T3), immediately after the program (T4), and at 1-year follow-up (T5). Participant-level self-reported risk for (early onset) depression and anxiety, self-reported and observed co-rumination, self- and friend-reported friendship quality, self-reported positive and negative affect, self-reported interpersonal responses to positive affect, and self-reported anhedonia symptoms will be the outcome ...