The increasing use of radiation-associated diagnostic and therapeutic procedures have contributed to the improvements of early diagnosis and survival of paediatric patients. While benefits to the patient outweigh the radiation associated risk, the late effects of exposure of children are particularly important to understand in populations with increased survival. The HARMONIC project builds on close collaboration between scientific and medical communities to contribute to improvements in the understanding of the health effects of medical ionising radiation exposure of paediatric patients, focusing on two distinct and complementary populations: (1) Paediatric patients undergoing modern radiotherapy (including proton therapy); (2) Paediatric patients undergoing interventional cardiology. Our project will provide additional insight into exposure to ionising radiation in childhood, exploring potential effects at very early ages, exposure to a wide range of doses from photons, protons and secondary neutrons radiation. We aim at building European cohorts and registries for long term follow-up of paediatric patients treated with ionising radiation, both in cardiology and oncology settings, in the context of very rapid technology evolution. The study will use an integrated approach of conventional epidemiology, based on state-of-the art dosimetry, complemented by non-invasive imaging and molecular epidemiology to assess the following outcomes: endocrine dysfunctions, cardio and neurovascular diseases, societal impact and cancer. Complementary to this effort, we propose to investigate radiation-induced cellular responses in samples of blood and saliva, and the mechanisms involved in the processes that may lead to cancer and vascular diseases. Ultimately, HARMONIC will develop tools and allow definition of guidelines on optimization techniques to guide treatments toward reduction of patient doses in paediatric cardiology and oncology.