[Abstract] Objective：To investigate the clinical characteristics and identify the associated factors in patients with atrial fibrillation (AF) and moderate to severe atrial functional mitral regurgitation (AFMR). Methods: This is a single-center, cross-sectional study. A total of 313 consecutive patients with AF and AFMR hospitalized in the Cardiovascular Department of The Affiliated Jiangning Hospital of Nanjing Medical University from July 2023 to March 2024. Patients were categorized into two groups based on the severity of mitral regurgitation: less than moderate AFMR group (Group A, n=249) and moderate to severe AFMR group (Group B, n=64). Baseline data were compared, and correlation analysis and logistic regression were employed to determine the factors associated with moderate to severe AFMR in AF patients. Results:Significant differences (P < 0.05) were observed between the groups in age, CHA2DS2-VASc score, history of renal insufficiency, heart failure with preserved ejection fraction (HFpEF), N-terminal pro-brain natriuretic peptide (NT-proBNP), tricuspid regurgitation severity, left atrial diameter, left ventricular end diastolic diameter, and left ventricular ejection fraction. Multivariate logistic regression analysis revealed that left atrial diameter (OR=1.067, 95% CI: 1.002-1.137, P=0.032), left ventricular end diastolic diameter (OR=1.153, 95% CI: 1.052-1.264, P<0.05), mild-to-moderate tricuspid regurgitation (OR=6.571, 95% CI: 3.816-30.543, P<0.05), moderate tricuspid regurgitation (OR=10.759, 95% CI: 3.816-30.543, P<0.05), moderate-to-severe tricuspid regurgitation (OR=19.525, 95% CI: 4.593-82.999, P<0.05), and severe tricuspid regurgitation (OR=20.701, 95% CI: 5.799-73.896, P<0.05) were independent risk factors for moderate tosevere AFMR in AF patients. Conclusion: Compared to AF patients with AFMR less than moderate severity, those with moderate to severe AFMR show the discrepancy in clinical characteristics, and they tend to exhibit a more complex clinical profile. Left atrial diameter enlargement, left ventricular end diastolic diameter enlargement, and the presence of more than mild severity of tricuspid regurgitation, are independent predictors of moderate to severe AFMR in AF patients.