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Background Left atrial (LA) enlargement is a predictor of worse outcome after catheter ablation for atrial fibrillation (AF). Widely used two-dimensional (2D)-echocardiography is inaccurate and underestimates real LA volume (LAV). We hypothesized that baseline clinical characteristics of patients can be used to adjust 2D-ECHO indices of LAV in order to minimize this disagreement. Methods The study enrolled 535 patients (59 ± 9 years; 67% males; 43% paroxysmal AF) who underwent catheter ablation for AF in three specialized centers. We investigated multivariately the relationship between 2D-echocardiographic indices of LA size, specifically LA diameter in M-mode in the parasternal long-axis view (LAD), LAV assessed by the prolate-ellipsoid method (LAVEllipsoid), LAV by the planimetric method (LAVPlanimetry), and LAV derived from 3D-electroanatomic mapping (LAVCARTO). Results Cubed LAD of 106 ± 45 ml, LAVEllipsoid of 72 ± 24 ml and LAVPlanimetry of 88 ± 30 ml correlated only modestly (r = 0.60, 0.69, and 0.53, respectively) with LAVCARTO of 137 ± 46 ml, which was significantly underestimated with a bias (±1.96 standard deviation) of -31 (-111; +49) ml, -64 (-132; +2) ml, and -49 (-125; +27) ml, respectively; p < 0.0001 for their mutual difference. LA enlargement itself, age, gender, type of AF, and the presence of structural heart disease were independent confounders of measurement error of 2D-echocardiographic LAV. Conclusion Accuracy and precision of all 2D-echocardiographic LAV indices are poor. Their agreement with true LAV can be significantly improved by multivariate adjustment to clinical characteristics of patients. [ABSTRACT FROM AUTHOR]