BACKGROUND: Dutch teachers in secondary vocational schools suffer from stress and burnout complaints that can cause considerable problems at work. This paper presents a study design that can be used to evaluate the short-term and long-term effectiveness of mindfulness-based stress reduction (MBSR), a person-focused intervention, both within and outside of the context of an additional organisational health intervention. METHODS: The proposed study comprises a cluster randomised controlled trial that will be conducted in at least three secondary vocational schools, to which teachers will be recruited from three types of courses: Care, Technology, and Economy. The allocation of the intervention programme to the participating schools will be randomised. The teachers from each school will be assigned to intervention group 1 (IG 1), intervention group 2 (IG 2), or the waiting list group (WG). IG 1 will receive MBSR training and IG 2 will receive MBSR training combined with an additional organisational health intervention. WG, that is the control group, will receive MBSR training one year later. The primary outcome variable of the proposed study is mindfulness, which will be measured using the Dutch version of the Five Facet Mindfulness Questionnaire (FFMQ-NL). In the conceptual model, the effects of teachers' mindfulness resulting from the intervention programmes (MBSR training and MBSR training combined with an additional organisational health intervention) will be related to salient (secondary outcome) variables: mental health outcomes (e.g., burnout, work engagement), work performance, work-related perceptions (job demands and job resources), and personal competencies (e.g., occupational self-efficacy). Data will be collected before (T DISCUSSION: The proposed study aims to provide insight into (1) the short-term and long-term effects of MBSR on teachers' mental health, (2) the possible enhancing effects of the additional organisational health intervention, and (3) the teachers' experiences with the interventions (working mechanisms, steps in the mindfulness change process). Strengths of this study design are the use of both positive and negative outcomes, the wide range of outcomes, both outcome and process measures, longitudinal data, mixed methods, and an integral approach. Although the proposed study protocol may not address all weaknesses of current studies (e.g., self-selection bias, self-reporting of data, the Hawthorne effect), it is innovative in many ways and can be expected to make important contributions to both the scientific and practical debate on how to beat work-related stress and occupational burnout, and on how to enhance work engagement and work performance. TRIAL REGISTRATION: Dutch Trial Register (www.trialregister.nl): NL5581. Registered on 6 July 2016.