Background: Atrial fibrillation (AF) is the most common etiology of acute ischemic stroke (AIS). In recent years, epicardial fat tissue (EFT) has been found to be associated with the presence and chronicity of AF. However, the potential association between EFT and AIS in AF patients has not been fully elucidated. The aim of this study was to evaluate the effectiveness of EFT on prediction of AIS in patients with AF. Methods: This cross-sectional study has included 80 AF patients with AIS and 80 age-gender matched AF controls without AIS. Echocardiographic evaluations were performed in the first three days after hospitalization between July 2019 and December 2019 in Sakarya University Education and Research Hospital. Echocardiographic measurement of EFT was conducted according to previously published methods. Results: In comparison with the control group, AF patients with AIS had significantly higher epicardial fat thickness (8.55 +/- 1.08 vs 5.90 +/- 1.35 mm; P < 0.0001). The multivariate regression analysis indicated that EFT independently predicts AIS in patients with AF. Conclusions: The present study showed that, EFT is an independent predictor for the development of acute ischemic stroke in patients with AF.