Background: Atrial fibrillation (AF) occurs due to various etiologies that carry different risks for thromboembolism. However, the effect of different etiologies on left atrial appendage (LAA) function has not been investigated. This study aimed to examine the LAA function in AF that occurred under various etiologies and to compare the findings with a novel tissue Doppler imaging (TDI) technique by using transesophageal echocardiography (TEE). Methods: LAA function was assessed in 84 patients with permanent AF according to various etiologies [mitral stenosis in 20 (24%), hypertension in 44 (52%), and hyperthyroidism in 20 (24%) patients] and in 23 controls with sinus rhythm. LAA area change, PW-Doppler and tissue velocities of LAA were measured. The presence of SEC or thrombus and their relation to LAA function was evaluated. Results: LAA velocities were lowest in mitral stenosis and highest in hyperthyroidism. Moderate-severe LAA SEC was detected in 61 and thrombi in 23 patients. Factors associated with the severity of SEC were the percentage of the LAA area change, PW-Doppler peak emptying velocity, and TDI septal wall downward velocity. The percent of the LAA area change and PW-Doppler peak emptying velocity were the significantly related factors for the presence of thrombi (OR = 0.84, 95% CI = 0.74-0.95, P = 0.005 and OR = 0.85, 95% CI = 0.74-0.98, P = 0.02, respectively). Conclusion: LAA function deteriorated most severely in mitral stenosis and least in hyperthyroidism. The LAA area change and PW-Doppler emptying velocity were important predictors for SEC or thrombi. Although TDI was not superior to classical methods, it provided complementary data to PW-Doppler velocities for predicting SEC and thrombi.