A prospective study was designed to investigate potential changes of left atrial (LA) spontaneous echo contrast with time and the effects of antithrombotic therapy on its presence in 77 patients with chronic nonrheumatic atrial fibrillation (AF), using serial transesophageal echocardiography (TEE). During a mean follow-up period of 20 +/- 15 months (range 6 to 77), a total of 197 TEE studies were performed in these patients. Baseline TEE revealed that LA spontaneous echo contrast was absent in 43 patients (group 1) and present in 34 (group 2). LA thrombus was found in 8 of group 2 but in none of the group 1 patients. During the follow-up period, only 2 of the group 1 patients were receiving antithrombotic agents; the patients in group 2 without LA thrombus were treated with either warfarin or aspirin, whereas those with LA thrombus were treated with warfarin. On the latest TEE study, LA spontaneous echo contrast was observed in 19 of the group 1 patients (44%) and was persistently found in all of the group 2 patients. During the study period, no patient was found to develop new LA thrombus formation and only 4 episodes of transient ischemic attack were recorded in 4 patients (embolic event rate = 3.1% per year). Of these, 2 were observed in group 1 and the remaining 2 were from group 2 and under aspirin therapy (event rate = 2.2% and 4.7% per year, respectively). In the subgroup of patients with LA thrombus receiving warfarin therapy, follow-up TEE revealed complete resolution of the thrombi in 6 and partial resolution in the remaining 2 in spite of the persistence of LA spontaneous echo contrast; none of these patients developed clinical thromboembolic events during the study period. Thus, future occurrence of LA spontaneous echo contrast could be observed by serial TEE at a substantial rate in patients with nonrheumatic AF who have no LA spontaneous echo contrast; follow-up TEE should be recommended for these patients to detect early the potential occurrence of LA spontaneous echo contrast if preventive antithrombotic therapy is not considered. Although warfarin therapy is associated with resolution of LA thrombus, neither warfarin nor aspirin is effective for suppressing the presence of LA spontaneous echo contrast in nonrheumatic AF.