Background: Mindfulness has shown positive effects on mental health, mental capacity and well-being among adult population. Among children and adolescents, previous research on the effectiveness of mindfulness interventions on health and well-being has shown promising results, but studies with methodologically sound designs have been called for. Few intervention studies in this population have compared the effectiveness of mindfulness programs to alternative intervention programs with adequate sample sizes. Methods/design: Our primary aim is to explore the effectiveness of a school-based mindfulness intervention program compared to a standard relaxation program among a non-clinical children and adolescent sample, and a non-treatment control group in school context. In this study, we systematically examine the effects of mindfulness intervention on mental well-being (primary outcomes being resilience; existence/absence of depressive symptoms; experienced psychological strengths and difficulties), cognitive functions, psychophysiological responses, academic achievements, and motivational determinants of practicing mindfulness. The design is a cluster randomized controlled trial with three arms (mindfulness intervention group, active control group, non-treatment group) and the sample includes 59 Finnish schools and approx. 3 000 students aged 12-15 years. Intervention consists of nine mindfulness based lessons, 45 mins per week, for 9 weeks, the dose being identical in active control group receiving standard relaxation program called Relax. The programs are delivered by 14 educated facilitators. Students, their teachers and parents will fill-in the research questionnaires before and after the intervention, and they will all be followed up 6 months after baseline. Additionally, students will be followed 12 months after baseline. For longer follow-up, consent to linking the data to the main health registers has been asked from students and their parents. Discussion: The present study examines systematically the effectiveness of a school-based mindfulness program compared to a standard relaxation program, and a non-treatment control group. A strength of the current study lies in its methodologically rigorous, randomized controlled study design, which allows novel evidence on the effectiveness of mindfulness over and above a standard relaxation program.