Background: Histological studies in animal models have showed that extensive atrial fibrosis or fatty deposition as a result of loss of atrial cardiomyocytes increases the propensity to develop atrial fibrillation (AF). Although several reports have suggested that AF in humans may be a consequence of these mechanisms, no study has correlated the presence of AF with interatrial septal thickness (IAST)., Methods: Accordingly, we conducted a prospective analysis in 150 consecutive patients referred for transesophageal echocardiography (TEE) for numerous medical reasons. A total of 105 patients (mean age 62 +/- 14 years) who met inclusion and exclusion criteria were included for analysis. Pertinent demographics, echocardiographic chamber dimensions, left ventricular ejection fraction (LVEF), color flow, and spectral Doppler analysis, as well as IAST measured in both systole (S) and diastole (D) were obtained., Results: When patients with a documented history of AF were compared to patients without documented AF, no statistical difference was noted in terms of patients' height, weight, IVS thickness, or LVEF. Patients with AF had a significantly larger left and right atrial dimensions (P < 0.001), lower left atrial appendage emptying velocities (P < 0.002), and pulmonary vein systolic Doppler signal (P < 0.01). The IAST in systole in patients with AF was 0.75 +/- 0.27 cm versus 0.60 +/- 0.16 cm in patients without AF (P < 0.006) while the IAST in diastole was 0.61 +/- 0.22 cm versus 0.49 +/- 0.12 cm, respectively (P < 0.009). However, no statistical difference was noted between IAST in either systole (P < 0.8) or diastole (P < 0.8) among patients with AF based on the duration of this arrhythmia., Conclusions: The results of this prospective TEE study show a statistically significant increase in IAST with the presence of AF independent of patient's age, height, weight, and the degree of IVS thickness. In addition, since no significant valvular abnormalities or compromise in left ventricular systolic function were present, the increase in IAST in patients with AF then suggest possible changes in the material properties of the atrial wall, easily identified by TEE on the interatrial septum, either as a cause or as a result of AF. Since no correlation was found between the degree of IAST and the duration of AF, the presence of IAST not only might identify patients with a higher propensity to have or develop this atrial arrhythmia; but also be a surrogate marker of changes within the components of the atrial wall in AF.