BACKGROUND Information on the association between γ-glutamyltransferase (GGT) and the incidence of atrial fibrillation (AF) is scarce. We evaluated the association between GGT and AF incidence, and the interaction between GGT and obesity on developing AF in a large population-based cohort. METHODS We evaluated 266,550 individuals (mean age, 53±11; men, 48.4%) who underwent the national insurance health checkup between 2004 and 2008. Subjects were categorized in accordance with quartiles of GGT levels (range: Q1, 0-15U/L; Q2, 16-22U/L; Q3, 23-38U/L; Q4, ≥39U/L). The association between GGT levels and AF incidence was analyzed by using multivariable Cox proportional-hazards regression models. RESULTS During a median of 8years' follow-up, 5034 individuals (1.9%) were newly diagnosed with AF. The crude AF incidence gradually increased with increases in GGT level (1.9, 2.5, 2.8, and 3.1 per 1000 person-years in the Q1, Q2, Q3, and Q4 GGT groups, respectively; p for trend <0.001). In the multivariable Cox proportional hazard models, GGT level showed a dose-response relationship with AF incidence. The subjects with the highest quartile of GGT levels had a significantly higher risk of AF (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.18-1.45; p<0.001). When the analysis was stratified by body mass index (BMI), GGT level showed good discrimination for AF incidence only in the non-obese population (BMI<25kg/m2), and not in the obese population (BMI≥25kg/m2; p interaction<0.001). CONCLUSIONS In this large population-based study, elevated GGT level showed a significant association with increased risk of AF, especially in a non-obese population.