Galectin-3 is known to play an important role in a number of fibrotic conditions, including cardiac fibrosis. Many studies have focused on the association between galectin-3 levels and cardiac fibrosis in heart failure. However, the role of galectin-3 in the pathogenesis of atrial fibrillation (AF) has not been evaluated thoroughly yet. The aim of this study was to determine whether serum galectin-3 levels were elevated in patients with AF and preserved left ventricular function. Seventy-six patients with paroxysmal or persistent AF and preserved left ventricular systolic function and 75 age- and gender-matched control subjects were enrolled in this observational study. Galectin-3 levels were measured by enzyme-linked immunosorbent assay. Serum galectin-3 (median 0.6 ng/ml [interquartile range 0.2 to 1.4] vs 0.5 ng/ml [interquartile range 0.1 to 0.7], p <0.001) and left atrial volume index (LAVI) (mean 29.5 ± 3.5 vs 26.5 ± 2.5 ml/m2, p <0.001) were significantly greater in patients with AF compared with the control group. Serum galectin-3 levels were also significantly higher in patients with persistent AF than those with paroxysmal AF (median 0.8 ng/ml [interquartile range 0.4 to 1.4] vs 0.5 ng/ml [interquartile range 0.2 to 0.9], p <0.001). Multivariate regression analysis demonstrated that serum galectin-3 (odds ratio 87.53, 95% confidence interval 6.06 to 1,265.03, p = 0.001) and LAVI (odds ratio 1.38, 95% confidence interval 1.19 to 1.60, p <0.001) were independent predictors of AF. Only LAVI was independently correlated with serum galectin-3 levels in patients with AF in linear regression analysis. In conclusion, serum galectin-3 is significantly elevated and is also significantly correlated with LAVI in patients with AF with preserved left ventricular function.