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The atrial septal pouch is an anatomic variant of the interatrial septum. The morphology of the left-sided septal pouch (LSSP) may favor blood stasis and predispose to thromboembolic events. The aim of this study was to determine the association between LSSP presence and cryptogenic stroke.A total of 126 consecutive patients with cryptogenic stroke and 137 age-matched control patients without stroke were analyzed retrospectively. The presence and dimensions of LSSPs were assessed using transesophageal echocardiography.LSSP was present in 55.6% of patients with cryptogenic stroke and in 40.9% of those without stroke (P = .02). In univariate analysis, patients with LSSP were more likely to have cryptogenic stroke (odds ratio, 1.81; 95% CI, 1.11–2.95; P = .02). After adjusting for other risk factors using multiple logistic regression, the presence of an LSSP was found to be associated with an increased risk for cryptogenic stroke (odds ratio, 2.02; 95% CI, 1.19–3.41; P = .01). There were no statistically significant differences in size of the LSSP between patients with and those without stroke (P > .05).There is an association between the presence of an LSSP and an increased risk for cryptogenic stroke. More attention should be paid to clinical evaluations of LSSPs.The authors demonstrate an association between the presence of LSSP and cryptogenic stroke.In patients with cryptogenic stroke, LSSP should be considered a possible site of thrombus formation.Large prospective trials are necessary to determine role of LSSP as an independent stroke risk factor.