Objective: To explore anatomic structure and function of left atrial appendage (LAA) in the risk assessment of cardiogenic stroke in patients with atrial fibrillation (AF). Methods: A total of 223 patients with non-valvular atrial fibrillation (NVAF), including 70 with and 153 without episodes of cardiogenic stroke, were enrolled in the study. The transthoracic and transesophageal echocardiography were retrieved and analyzed along with clinical data. Results: Between subjects with and without episodes of stroke, there were significant differences in demographic and laboratory parameters, including age, prevalence of hypertension or diabetes, glomerular filtration rate, atrial size of both sides, opening inner diameter of each angle of LAA, depth of the LAA, ratio of the depth/opening inner diameter, spontaneous echo contrast (SEC) in LAA and the blood flow (P<0.05). Patients with cactus- or cauliflower-shaped LAA had a higher incidence of stoke than those with wing- or wind vane-shaped LAA. Multivariable logistic regression analysis showed that higher sum of opening inner diameters and higher blood flow velocity in LAA were protective factors against stroke, and the higher sum of depths in LAA was an independent risk factor for stroke. When the cutoff values for the sum of opening inner diameters, the blood flow velocity and the sum of depths in LAA were set as≤71 mm, ≤41 cm/s and≥103 mm, the sensitivity and specificity of each parameter for stroke predication were 91% and 83%, 79% and 46%, 74% and 89% respectively. Conclusion: The incidenceof cardiogenic stroke is associated with anatomic features of LAA, such as cactus- or auliflower-shaped LAA, the sum of opening inner diameters and depths of LAA, and blood flow velocity in LAA. Evaluation of anatomy and function of LAA might facilitate stroke prediction as a supplement of CHA₂DS₂VASc score in patients with AF.