Introduction: Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical, and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and genetic profiles. Methods and analysis: EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1,500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will give a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent for the study to access pre-existing clinical data. Participants will be added to the EAGER registry. Data will be shared via the Autism Sharing Initiative, a new international collaboration aiming to create a federated system for autism data sharing. Ethics and dissemination: EAGER has received full ethical approval from ethics committees in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023) and Spain (HCB/2023/0038, PIC-164-22). Approvals are in the process of being obtained from committees in Italy, Sweden, Ireland, and France. Findings will be disseminated via scientific publications and conferences, but also beyond to participants and the wider community (e.g., the AIMS-2-TRIALS website, stakeholder meetings, newsletters).