Left atrial appendage (LAA) thrombus in nonvalvular atrial fibrillation or flutter (AF) is a major cause of stroke and presents a therapeutic dilemma in a rhythm-control strategy. The prevalence and resolution of LAA thrombus has not been studied well in the era of non-vitamin K antagonist oral anticoagulant use. This study sought to establish (1) the prevalence of LAA thrombus (2) the prevalence of LAA thrombus despite antithrombotic therapy, (3) the rate of persistence of LAA thrombus despite appropriate anticoagulant prescriptions, and (4) determinants of LAA thrombus persistence. Consecutive transesophageal echocardiograms (TEE) performed in patients with AF were reviewed to estimate the overall prevalence of LAA thrombus and the resolution rate in those with repeat studies. Multivariable logistic regression was used to identify clinical and echocardiographic predictors of thrombus resolution. Of 1,485 patients with AF, 117 (8%) had LAA thrombus. Of those, 62 had repeat TEE within 1 year and 58 (94%) were prescribed adequate anticoagulation in TEE studies (mean interval 96 ± 72 days). Thirty-seven patients (60%) had LAA thrombus resolution. Thrombus resolution rate was only 79% in patients considered on appropriate anticoagulation. Patients with persistent LAA thrombus were more likely to have diabetes; no other clinical or echocardiographic variable was independently associated with thrombus resolution. There was no significant difference in LAA thrombus resolution between non-vitamin K antagonist oral anticoagulants and warfarin. LAA thrombus persistence despite adequate anticoagulation is relatively common and difficult to predict clinically; TEE before electrical cardioversion should be considered regardless of anticoagulation status.