OBJECTIVES: We sought to validate the safety of transesophageal echocardiographically guided early cardioversion in conjunction with short-term anticoagulation as a strategy for guiding early cardioversion in hospitalized patients with atrial fibrillation. BACKGROUND: Because atrial thrombi are poorly seen by conventional imaging techniques, several weeks of prophylactic anticoagulation is routinely prescribed before cardioversion. Transesophageal echocardiography is a superior test for identifying atrial thrombi; preliminary feasibility studies have supported its use to guide early cardioversion for patients in whom no thrombus is observed, but safety has not been validated in any large series. METHODS: All patients admitted to hospital with atrial fibrillation during a 4.5-year period were screened. The inclusion criterion was a clinical duration of atrial fibrillation > 2 days or of unknown duration. Patients received anticoagulation with heparin/warfarin and underwent conventional transthoracic echocardiography followed by transesophageal study. Patients in whom transesophageal echocardiography revealed no atrial thrombus underwent pharmacologic or electrical cardioversion followed by warfarin therapy for 1 month. Cardioversion was deferred in patients with evidence of atrial thrombi, and they received prolonged warfarin treatment. RESULTS: Two hundred thirty-three patients (86% of those eligible) agreed to participate, and 230 underwent transesophageal echocardiography. Transesophageal echocardiography identified 40 atrial thrombi (left atrium 34, right atrium 6) in 34 patients (15%). One hundred eighty-six (95%) of 196 patients without thrombi had successful cardioversion to sinus rhythm, all without prolonged anticoagulation, and none (0%, 95% confidence interval 0% to 1.6%) experienced a clinical thromboembolic event. Eighteen patients with atrial thrombi underwent uneventful cardioversion after prolonged anticoagulation. CONCLUSIONS: Compared with smaller series that have shown only feasibility, this large prospective and consecutive study of patients undergoing transesophageal echocardiographically facilitated early cardioversion in conjunction with short-term anticoagulation validates the safety of this strategy. This treatment algorithm has a safety profile similar to conventional therapy and minimizes both the period of anticoagulation and the overall duration of atrial fibrillation.