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Introduction Atrial fibrillation (AF), the most common sustained arrhythmia globally, necessitates effective strategies for stroke prevention. Although current risk stratification tools, such as the CHA₂DS₂-VASc score, are widely used to guide anticoagulation therapy, their limited predictive accuracy underscores the urgent need for more precise and reliable models. This study aims to establish a nationwide AF registry incorporating multi-dimensional data to identify novel risk factors and develop a more accurate stroke prediction model to improve risk stratification and guide anticoagulation therapy in patients with AF.Methods/analysis The risk factors for stroke in patients with non-valvular AF in China (REFINE) registry is a nationwide, multicentre, observational registry integrating retrospective (n=20 000) and prospective (n=5000) cohorts. Demographics, lifestyle, medical history, physical examination, laboratory tests, ECG, echocardiography, contrast-enhanced CT scan and blood samples will be collected at baseline. Long-term follow-up will be performed to identify clinical events and treatment at the timepoint. We aim to use the multidimensional dataset to establish a more precise stroke risk predictive tool.Ethics and dissemination The study is approved by the Ethics Committee of Fuwai Hospital, CAMS&PUMC (No. 2022–1845; No. 2024–2489) and registered at ClinicalTrials.gov, identifier NCT05598632. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration number NCT05598632.