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Introduction: Recent studies have consistently reported that gamma-glutamyl transferase (GGT) is correlated with higher risk of stroke independent of stroke risk factors and alcohol intake. However, it remains to be further elucidated why GGT is associated with stroke. To clarify the question, we focused on atrial fibrillation (AF), which has also been noted to have a close relationship with GGT.Hypothesis: GGT may be associated with cardioembolic stroke through AF.Methods: From a prospective stroke registry of Seoul National University Hospital, acute ischemic stroke patients who had checked GGT within 7 days from the admission were selected for analysis. The binary logistic regression was used to investigate the relationship between GGT, AF, and cardioembolic stroke.Results: Among 958 eligible patients, 134 patients (13.99%) had AF and 269 (28.08%) patients were classified as cardioembolism according to the TOAST system. GGT was significantly associated with AF in ischemic stroke patients (Adjusted OR, 2.43; 95% CI, 1.32-4.52). Patients with elevated GGT were more likely to be assigned to cardioembolism compared to other TOAST classifications, after adjustment for all potential confounders except for AF (OR, 2.14; 95% CI, 1.31-3.52). When an additional adjustment for AF was made, the increasing trend in OR according to increasing GGT quartile was lost and the association between GGT and cardioembolism was considerably attenuated, although the relationship remained significant (OR, 1.79; 95% CI, 1.01-3.2).Conclusions: GGT showed significant correlation with cardioembolic stroke, potentially owing in large part to its relationship with AF. It may be a possible answer to explain the association between GGT and stroke.