Background Rare diseases (RDs) affect nearly 3 million people in France and at least 26-30 million people in Europe. These diseases, which represent a major medical concern, are mainly of genetic origin and account for more than one third of all deaths occurring during infancy. In this context, there are needs for coordinated information on RDs at national/international levels, based on high quality sharable data. The RaDiCo (Rare Disease Cohorts) program, which has been selected by the “Cohorts” call from the “Programme Investissements d’Avenir“ (PIA1) received its initial funding in 2012. The main objective of this program coordinated by Inserm was to create a national operational platform dedicated to the development, within a research framework, of several RD e-cohorts that meet strict criteria of excellence. The RD e-cohort projects were selected through a RaDiCo’s national call in 2014 (international evaluation–success rate: 25%). Depending on cohorts, the objectives were to describe the natural history of the studied RD(s), identify the underlying disease genes, establish phenotype-genotype correlations, decipher their pathophysiology, assess their societal/medico-economic impact, and/or identify patients eligible for new therapeutic approaches. Results A platform equivalent to an infrastructure has been set up ex-nihilo. It pools all the resources needed for implementing within an industrialization framework a RD database. Constructed on the "cloud computing" principle, the plateform, which relies on an original Information System (IS), is in compliance with the European directive on General Data Protection Regulation (GDPR), ensuring a continuous monitoring of data quality. As of September 2021, more than 6000 patients have been included within 13 RD e-cohorts covering 67 diseases integrated in 10 European Reference Networks and contributing to the European Joint Program on RDs. Several original results published in ~40 peer-reviewed international journals have been obtained in relation with the secondary objectives of the cohorts. They deal with discovery of new disease genes, assessment of treatment management, deciphering the underlying pathophysiological mechanisms, diagnostic approaches, genotype-phenotype relationships, development of questionnaires relative to disease burden, or methodological aspects. Conclusion The RaDiCo program promotes the collection of RD data of different types for epidemiological and clinical research purposes in connection with basic and translational research. The RaDiCo platform offers a common core of services to ensure installation and follow-up of RD e-cohorts, as well as an IS that, as it can drive a virtually unlimited number of e-cohorts, has become the base of the IS of the “France Cohortes” Inserm unit that includes cohorts of common disorders and population-based cohorts. Currently, 13 RD e-cohorts are implemented in RaDiCo and other national, European and international cohorts are targeted.