Objective: Our objective was to compare the utility of combined two-dimensional (2D) transthoracic echocardiography (TTE) and three-dimensional (3D) TTE versus 2D transesophageal echocardiography (TEE) in evaluation of the left atrium (LA) and LA appendage (LAA) for clot. Background: 2DTEE, usually performed to visualize the LAA, is semi-invasive and not without risks. With improved technology the LAA has been increasingly visualized by 2DTTE and 3DTTE in many patients. Methods: We compared combined 2DTTE and 3DTTE with 2DTEE in evaluating the LA/LAA for a thrombus. Ninety-two patients underwent 2DTTE, 3DTTE, and 2DTEE. An additional 20 patients, in whom TEE could not be performed, underwent 2DTTE and 3DTTE. Results: LA and LAA could be visualized in all patients. Of 92 patients studied, 74 had no thrombus and 7 had thrombus in the LAA by all modalities. Eleven patients, 9 with atrial fibrillation (AF), had a suspected thrombus by 2DTEE, but 3DTTE cropping clearly showed these to be prominent pectinate muscles which were seen in short axis on 2DTEE as rounded echo dense masses and therefore mimicked thrombi. These 9 patients with AF underwent successful cardioversion without any complications. Of the 20 patients in whom TEE could not be performed, 19 had no thrombus in the LA/LAA and 1 had a clot in the LAA. These 19 patients underwent successful cardioversion without complications. Conclusions: Our preliminary study suggests that combined 2DTTE and 3DTTE has comparable accuracy to TEE in evaluating the LA and LAA for thrombus. In some patients TEE, but not 3DTTE, may misdiagnose pectinate musculature as thrombus.