Background The gap between the supply and demand of organ donors is substantial, causing patients to suffer from long waiting times. Moreover, the lack of registrations places a burden on family members and medical professionals when an unregistered individual dies. This article describes a cluster randomized controlled trial (CRCT) study to assess the effectiveness and quality of implementation of a web-based program aimed at encouraging lower-educated adolescents to register a well-informed choice about organ donation, regardless of it being as a donor or not. Methods/design The program will be delivered by teachers at schools for Intermediate Vocational Education in the Netherlands. The effectiveness will be assessed in a CRCT design with post-test only using self-administered questionnaires for the primary outcome (i.e. intention to register). Classes will be matched to improve equivalence of groups. From each pair of matched classes, one class will be randomly assigned to the experimental condition, and the other assigned to the control condition. Students in the control groups will fill in the questionnaire before receiving the program, while the experimental groups will do this afterwards. A post-test design prevents the risk of testing bias. The required sample size is 14 schools, with 10 classes per school and 13 unregistered students per class. The questionnaire assesses demographics, behavioural determinants (attitude, self-efficacy, knowledge and social outcomes), intention to register (as a donor) and registration status. Six months after delivery, registration status will be assessed again. Additionally, a process evaluation will be conducted to evaluate the quality of implementation using both qualitative (i.e. semi-structured interviews) and quantitative (i.e. logbooks, questionnaires, Google Analytics to track user behaviour at the website) methods. Discussion Findings of the study can help to further improve the program and serve as a basis for a solid dissemination plan. Moreover, the study will provide insight into (change in) determinants of registration and donorship and the translation of research into practice of school-based health promotion interventions, which can serve as an example for others. Trial registration The Dutch Trial Register, NTR6771. Registered on 24 October 2017. This is version 2 of the protocol (5 November 2017). Electronic supplementary material The online version of this article (10.1186/s13063-018-2927-6) contains supplementary material, which is available to authorized users.