Abstract Background/Introduction Atrial fibrillation (AF) presents a significant global health burden, affecting millions and associated with elevated risks of mortality, heart failure, and stroke despite current treatment strategies. The current diagnosis of AF relies on episode characteristics, yet its heterogeneity calls for personalized assessment incorporating clinical features, biomarkers, and substrate determination for improved classification and management. Purpose This study aimed to develop a refined classification of AF according to comprehensive risk factors to identify patients at high-risk for poor prognosis and their life expectancy, aiming to facilitate personalized interventions. Methods A total of 7,391 participants aged 40-69 with AF at baseline, from UK Biobank, were recruited in the main analyses. Firstly, LASSO regression with Cox model and factor analysis were adopted for identification and integration of principal risk factors. Second, Consensus clustering analysis was employed to estimate the optimal cluster number and group all 7,391 participants. Difference in the risk of death and major complications, as well as reductions in life expectancy, among clusters were estimated. Replication was done in 2,399 participants with newly diagnosed AF within two years after baseline. Results Risk factors for AF were categorized into seven aspects (metabolic factors, respiratory factors, cardiovascular factors, renal and immunity diseases, mental health, acute illness, age), based on the correlation between them. Five distinct AF clusters were identified according to these seven characteristics: acute illness-related (Cluster 1), mental health-related (Cluster 2), cardiovascular disease-related (Cluster 3), immune-and-renal disease-related (Cluster 4), and respiratory-and-metabolism disease-related AF (Cluster 5). Patients with respiratory-and-metabolism disease-related AF had the highest risk of death, acute myocardial infarction, heart failure, and cerebral ischemic stroke, while those with acute illness-related AF had the lowest corresponding risk. In addition, compared with individuals with acute illness-related AF, those with respiratory-and-metabolism disease-related and mental health-related AF had the top 2 greatest loss of life expectancy. Furthermore, genetic variants for AF had different effect among the five clusters. Replication analysis confirmed the result stability. Conclusion A novel AF classification was developed, which provided insights into varying life expectancy and risks of death and complications among AF subgroups with distinct characteristics. It offers a practical approach for identifying high-risk patients, which may help to tailor precise interventions for AF management.Graphic abstractCluster features