Abstract Background Organ donation registration rates remain low, especially among people with lower educational levels. An interactive educational intervention was developed to prepare lower-educated students in the Netherlands for making a well-informed decision about organ donation. This article reports on the effects of this intervention on the intention to register (i.e., the primary outcome in the study at hand) and beliefs regarding organ donation. Materials and methods The effectiveness was investigated in a post-test-only cluster randomized controlled trial, in which the intervention was offered to the experimental group and after measurement also to the control group. Randomization to the experimental and control groups took place at a class level. Teachers of schools for Intermediate Vocational Education who taught a course on Citizenship delivered three intervention elements (i.e., video fragments and discussion, quizzes with tailored feedback and exercise filling out a registration form) to their students during two 50-min lessons. Results A total of 1170 students participated in the trial and filled out a questionnaire (45 experimental and 43 control classes). Compared to the control group, students in the experimental group had higher odds of having positive registration intentions (OR = 1.81; 95%CI [1.10–2.96]), their perceived knowledge was higher (B = 0.62; 95%CI [0.23–1.01]) and they had higher intentions to talk to family members (B = 0.68; 95%CI [0.28–1.08]) and friends (B = 0.36; 95%CI [0.07–0.66]) about organ donation. There were no effects on the choice students intended to register (OR = 1.08; 95%CI [0.67–1.73]). Conclusions Providing education in a classroom setting is an effective tool in increasing registration intentions. Despite uncertainties about the effects on actual registration behavior, a larger-scale dissemination of this intervention is recommended. Providing clear information and opening the discussion about organ donation is an important and promising first step towards ...