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Introduction: Despite extensive evaluation, no definite cause is identified in 30-40% of ischemic stroke patients. Biomarkers of atrial dysfunction or “cardiopathy” have been shown to be associated with ischemic stroke risk, a relationship independent of atrial fibrillation. Our aim was to determine the association between left atrial enlargement (LAE) and cryptogenic stroke.Methods: This was a single center retrospective study using the stoke registry of a comprehensive stroke center. The study was approved by the institution board review. We reviewed medical records of patients admitted with acute ischemic stroke between December 1st, 2013 and August 31st, 2015 for demographic data (age and sex) and risk factors (hypertension, hyperlipidemia, coronary artery disease, prior stroke, congestive heart failure, and current smoking status). A vascular neurologist determined stroke subtype and cryptogenic stroke was defined based on the embolic stroke of unknown source (ESUS) criteria. Patients with cardioembolic stroke were excluded and the control group included small vessel disease, large vessel disease and other causes including hypercoagulable states, dissection and drug use. The primary predictor was left atrial (LA) size from 2D echocardiography and LA size was categorized as normal, mild LAE, moderate LAE, and severe LAE using the American Society of Echocardiography Recommendations for chamber quantification.Results: We identified 236 patients with ischemic stroke; 85 cryptogenic stroke and 151 non-cryptogenic stroke. For the entirety of the group, the mean age was 67 years with 45% males. Patients with cryptogenic stroke were more likely to have moderate to severe LAE when compared to patients with known non-cardioembolic etiology (12.8% vs. 3.2%, p = 0.0061).Conclusion: Moderate to severe left atrial enlargement, a biomarker of atrial cardiopathy or dysfunction, is more prevalent in patients with cryptogenic stroke than non-cardioembolic strokes of known etiology. Clinical trials are needed to study anticoagulation vs. antiplatelet therapy in patients with cryptogenic stroke and evidence of moderate to severe LAE.