Removal precancerous polyps (so-called adenomas) during colonoscopy reduces colorectal cancer incidence and mortality. We have recently developed artificial intelligence (AI) systems which optimise colonoscopy quality by aiming at increasing the detection of adenomas. However, it is unknown if this benefit of AI translates into improved cancer prevention. To establish the role of AI in colorectal cancer prevention, we here propose a three-step research portfolio targeting individuals in the national colorectal cancer screening programmes in Norway and Poland. 1) A 1-year observational study to clarify the superiority of AI in adenoma detection in the average-risk population. 2) A cost-effectiveness analysis for cancer prevention, using real-world data obtained from the part 1 study. 3) Establishment of an infrastructure for long-term (10 years) follow-up of 40,000 individuals to quantify the effect of AI on colorectal cancer incidence. We use propensity score matching to balance the background characteristics of the two comparing arms; AI-assisted colonoscopy and standard colonoscopy. Participants are followed through national cancer registries for ten years after cancer screening. Our project is the first of its kind and made possible by the unique collaboration of world-class environments in clinical epidemiology and medical device assessment with world-leading AI developers. The project will enable evidence-based implementation of AI technologies into nationwide cancer screening programmes in Europe and the world. The project’s achievement will be maximised through detailed plans for training, monitoring, management, exploitation, dissemination, and communication. While adding essential competence to the host institution, this project will increase the applicant’s skill, especially in epidemiologic aspects, helping him obtain an independent academic position in translational research of AI for medicine.