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Introduction: The presence of spontaneous echo contrast (SEC) on transesophageal echocardiography (TEE) is associated with increased thrombogenecity and a risk factor of thromboembolism. The increased thrombogenecity in SEC may produce larger intracardiac thrombi, which result in larger cerebral infarctions and severe stroke.Hypothesis: We hypothesized that infarction volume will be larger in stroke patients with SEC than in those without SEC.Methods: This was a post-hoc analysis using a prospective cohort of acute ischemic stroke. This study included patients with nonvalvular atrial fibrillation (NVAF) who underwent TEE and diffusion weighted imaging (DWI) from Jan. 2008 to Dec. 2014. The volume of cerebral infarction on DWI was measured semi-automatically using 3-dimensional software by an investigator who was blinded to clinical information. The infarction volume was compared between patients with SEC and those without.Results: Of 4252 considered patients, 889 patients had NVAF. After excluding 449 patients without TEE and 39 patients without DWI, 401 patients were included for analysis. Of them, SEC was found in 181 patients (45.1%, 82 mild, 35 moderate, and 64 severe SEC). Infarction volume was larger for the patients with SEC than those without SEC (median [interquartile range], 7226.8 mm3 [1218.1-28804.6] vs. 4756.8 mm3 [672.8-14887.8], p=0.015). Infarction volume also increased with SEC severity (p=0.006). Initial National Institute of Health Stroke Scale scores were higher for the patients with SEC than those without SEC (median [interquartile range], 5.0 [2.0-12.0] vs. 3.0 [1.0-8.0]. p=0.008). On multivariate analysis, infarction volume was independently associated with the presence of SEC (p=0.014).Conclusion: Among stroke patients with NVAF, those with co-existing SEC had larger cerebral infarction, which may account for severe stroke. This may be related with increased thrombogenecity in patients with SEC.