Objective: To explore serum caveolin-3 (Cav-3) levels in patients with atrial fibrillation (AF) and to evaluate the role of Cav-3 as a biomarker for AF and incident heart failure (HF). Methods: Three hundred and five patients were enrolled in the study and divided into three groups: sinus rhythm (Group SR), paroxysmal AF (Group paAF), and persistent AF (Group peAF). Serum Cav-3 concentrations were measured by enzyme-linked immunosorbent assay at baseline. Clinical characteristics, and laboratory data were collected during hospitalization, and a follow-up of 12-months was carried out. Results: Serum Cav-3 concentrations were significantly decreased on the Group SR and the highest concentrations of Cav-3 in patients were found on the Group peAF (516.7 +/- 274.0 vs. 609.3 +/- 287.0 vs. 688.3 +/- 264.6 ng/L, P= 703). In further tertile studies, subjects in the lower tertile of Cav-3 concentrations were more likely to become paroxysmal AF and had much lower LAD (P < 0.05). And in the middle and upper tertiles, participants with AF tended to suffer from HF compared to the lower group (P < 0.05). Conclusion: We provide evidence that Cav-3 has a significant meaning in AF patients. The levels of Cav-3 may be related to the LAD and new-onset HF.