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Atrial fibrillation is the most common heart disease. Previous research has found that several members of the matrix metalloproteinase (MMP) family are involved. However, the role of the most recently discovered member of the MMP family, MMP-28, has not been fully investigated. The present study aimed to reveal the role of MMP-28 in atrial fibrillation.254 patients with sinus rhythm, paroxysmal atrial fibrillation, or persistent atrial fibrillation were enrolled in this prospective observational study. Circulating MMP-28, echocardiography, and other clinical variables were measured at hospital admission. Patients were followed for up to 7 months, and the end-point was occurrence of heart failure.MMP-28 was significantly higher in patients with atrial fibrillation than with sinus rhythm, and MMP-28 level was correlated with left atrial diameter. Additionally, MMP-28 independently predicted follow-up heart failure. Other clinical risk factors were previous myocardial infarction, brain natriuretic peptide, persistent atrial fibrillation, and left atrial diameter. MMP-28 increased the performance of prognostic prediction of heart failure.Circulating MMP-28 was elevated in atrial fibrillation. MMP-28 may be related to atrial fibrillation and heart failure.