Background: Implementing RD cohorts is a challenge since RDs are seldom, often underdiagnosed and spread over the national territories. Objective: To create a national platform dedicated to the development, within a research framework, of RD e-cohorts meeting strict criteria of excellence.Material and Methods: The RaDiCo program coordinated by Inserm comprises an operational platform and several RD e-cohorts. The platform, built on the "cloud computing" principle, is oriented as an “Infrastructure as a Service”; Interoperable; In compliance with the General Data Protection Regulation; Within a Certified Health Data Host; Ensuring continuous monitoring of data quality and consistency; In line with the French Health Data Hub.Results: 13 e-cohorts projects covering 67 RDs have been selected through a national call and launched (2017). Depending on cohorts, they aim at: Describing RDs’ natural history; Establishing phenotype-genotype correlations; Deciphering RDs’ pathophysiology; Identifying new therapeutic avenues; Assessing RDs’ societal and medico-economic impact; Identifying patients eligible for new therapeutic approaches. As of June 15, 2019, 4035 patients have been included and 1560 were eligible to come (recruitment target 97%); 26 publications appeared in international peer-reviewed journals.Discussion: Several secondary objectives of the e-cohorts have been reached. Member of the 3rd RDs’ National Plan, RaDiCo is tightly linked to patients’ associations and advocacy groups. Partnerships with industry confirm RaDiCo’s sustainability. The cohorts’ PIs are involved in 10 European Reference Networks. RaDiCo participates to the RD-European Joint Program.Conclusion: RaDiCo provides a flexible and easily sharable platform enabling the creation and follow-up of national/international RD e-cohorts.