Background Transesophageal echocardiography-guided direct cardioversion is recommended in patients who are inadequately anticoagulated due to perceived risk of left atrial appendage thrombus (LAAT); however, LAAT risk factors remain poorly defined. Methods and Results We evaluated clinical and transthoracic echocardiographic parameters to predict LAAT risk in consecutive patients with atrial fibrillation (AF)/atrial flutter undergoing transesophageal echocardiography before cardioversion between 2002 and 2022. Regression analysis identified predictors of LAAT, combined to create the novel CLOTS-AF risk score (comprising clinical and echocardiographic LAAT predictors), which was developed in the derivation cohort (70%) and validated in the remaining 30%. A total of 1001 patients (mean age, 62±13 years; 25% women; left ventricular ejection fraction, 49.8±14%) underwent transesophageal echocardiography, with LAAT identified in 140 of 1001 patients (14%) and dense spontaneous echo contrast precluding cardioversion in a further 75 patients (7.5%). AF duration, AF rhythm, creatinine, stroke, diabetes, and echocardiographic parameters were univariate LAAT predictors; age, female sex, body mass index, anticoagulant type, and duration were not (all >0.05). CHADSVASc, though significant on univariate analysis (<0.001), was not significant after adjustment (=0.12). The novel CLOTS-AF risk model comprised significant multivariable predictors categorized and weighted according to clinically relevant thresholds (Creatinine >1.5 mg/dL, Left ventricular ejection fraction <50%, Overload (left atrial volume index >34 mL/m), Tricuspid Annular Plane Systolic Excursion (TAPSE) <17 mm, Stroke, and AF rhythm). The unweighted risk model had excellent predictive performance with an area under the curve of 0.820 (95% CI, 0.752-0.887). The weighted CLOTS-AF risk score maintained good predictive performance (AUC, 0.780) with an accuracy of 72%. Conclusions The incidence of LAAT or dense spontaneous echo contrast precluding cardioversion in patients with AF who are inadequately anticoagulated is 21%. Clinical and noninvasive echocardiographic parameters may identify patients at increased risk of LAAT better managed with a suitable period of anticoagulation before undertaking cardioversion.P