The incidence of cerebrovascular events (CVEs) was investigated in 95 consecutive patients with atrial fibrillation (AF) with left atrial thrombus (LAT) diagnosed by transesophageal echocardiography (TEE) and in 131 age- and sex-matched AF patients without LAT. Compared with patients without LAT, patients with LAT had a larger left atrial diameter (49 versus 44 mm, P < 0.0001), a lower left ventricular ejection fraction (40% versus 50%, P < 0.0001), a higher prevalence of spontaneous echocardiographic contrast (88% versus 25%, P < 0.001), a reduced left atrial appendage emptying velocity (0.25 versus 0.41 cm/s, P < 0.0001), and less use of antiarrhythmic drugs (61% versus 76%, P = 0.03). Before TEE, the prevalence of prior CVE was higher in LAT patients (20%) compared with patients without LAT (8%) (P = 0.01). Fifty-four of 95 LAT patients (57%) and 81 of 131 non-LAT patients (62%) were on warfarin before TEE. The incidence of prior CVE in LAT patients without warfarin (32%) was higher than that in non-LAT patients without warfarin (10%) (P = 0.02). The mortality rate in LAT patients with an international normalized ratio (INR) >or= 2.0 (42%) was higher than that in patients without LAT and an INR >or= 2.0 (11%) (P < 0.001). Fifty-one of 95 LAT patients (54%) underwent repeat TEE before cardioversion (48 patients received warfarin therapy). The thrombus resolved in 40 of 51 patients (78%) after the first TEE. There was no significant difference in INR between the patients with persistent and resolved LAT. AF patients with persistent LAT had a higher incidence of CVE (45%) than the patients with resolved LAT (5%) (P = 0.003). We suggest that patients with LAT be treated with warfarin to maintain an INR between 2.5 and 3.5 rather than between 2.0 and 3.0 because they are at a high risk for new thromboembolism.