Patients with left atrial thrombus are considered at high risk for thromboembolic events. The actual prognosis of these patients and the features most predictive of future events are unclear. We performed transesophageal echocardiograms in 2,894 patients over a 6 1/2-year period; 94 (age 69 +/- 11 years, 59 men, 83 in atrial fibrillation) were found to have left atrial thrombus. The thrombi were considered mobile in 45 patients and 33 patients had thrombus with a maximum dimension > or = 1.5 cm. Seven of the 94 patients with prosthetic valves were excluded from follow-up analysis. Over a follow-up period of 25.3 +/- 19.2 months, 17 patients had suffered a stroke or embolic event (event rate 10.4% per year) and 27 had died (mortality 15.8% per year). Cox proportional hazard regression analysis identified a maximum thrombus dimension > or = 1.5 cm (RR 19, p = 0.002), history of thromboembolism (RR 4.2, p = 0.038), and mobile thrombus (RR 5.3, p = 0.02) as predictors of subsequent thromboembolism. Moderate or severe left ventricular dysfunction was the only significant predictor of death (RR 2.9, p = 0.04). Gender, age, warfarin therapy at follow-up, atrial fibrillation, location (cavity vs appendage) of thrombus, and spontaneous echocardiographic contrast were not significant. Aggressive antithrombotic therapy may be indicated in these high-risk patients.