Patients with atrial fibrillation (AF) undergoing cardioversion are at an increased risk of cardioembolic stroke and require anticoagulation. The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) Multicenter Study is a randomized clinical trial of patients undergoing electrical cardioversion of AF of >2 days' duration comparing a transesophageal-guided strategy (TEE) with brief anticoagulation to the conventional anticoagulation strategy. Patients randomly assigned to the TEE- guided strategy receive therapeutic anticoagulation before TEE and cardioversion, followed by 4 weeks of anticoagulation. Patients with thrombus imaged by TEE have postponement of cardioversion, continue anticoagulation for 3 weeks, and undergo a repeat TEE. Conventional strategy patients receive 3 weeks of anticoagulation before cardioversion, followed by 4 weeks of anticoagulation after cardioversion. The primary end point events are ischemic stroke, transient ischemic attack, and systemic embolization for an 8-week period from enrollment. Secondary end points are major and minor bleeding, all-course mortality, successful return to and maintenance of sinus rhythm, and cost effectiveness. Analysis is based on the intention-to-treat principle. The anticipated rates of embolism of 2.9% for conventional strategy and 1.2% for the TEE-guided strategy are based on published research and the completed pilot study. The ACUTE Multicenter Study will randomize therapy and follow an estimated 3,000 patients from 65 study sites to determine the relative efficacy of the TEE-guided and conventional approaches to electrical cardioversion for patients in AF. The results of this investigation will have important clinical implications for the management of patients with AF undergoing electrical cardioversion.