Abstract Background Timely detection of thrombus in the left atrial appendage (LAA) may help guide decision-making. However, existing models have challenges in extracting comprehensive image information. It has been shown that radiomics-based prediction models can be used for accurate identification. This study investigates potential radiomic markers and constructs a highly efficient multimodality prediction model for LAA thrombus in patients undergoing coronary computed tomography angiography (CCTA). Methods We retrospectively enrolled patients with nonvalvular atrial fibrillation (NVAF) who underwent CCTA and transesophageal echocardiography (TEE) from May 2015 to May 2020. These patients were classified into thrombus or non-thrombus groups based on TEE findings. The data were balanced by resampling and assigned to training or test sets. Radiomics was conducted on the extracted features, and a random forest algorithm was employed for feature selection and importance ranking. We constructed different multimodality thrombus prediction models and compared their performance using the area under the receiver operating characteristic curve (AUC) and other efficacy parameters. Results Among 670 patients (60.17±10.98 years, 70.1% male), 5.2% (n=35) had LAA thrombi. A total of 1232 radiomics features were extracted, with 25 features selected using a random forest for modeling. Two radiomics features (Ibp_3D_m1_firstorder Skewness and original_shape_Flatness) ranked the highest. The radiomics-based multimodality prediction model achieved an AUC of 0.964 (95% confidence interval [CI]: 0.947-0.982), an accuracy of 0.926 (95% CI: 0.925-0.926), and an F1 score of 0.924, outperforming other traditional prediction models. Decision curve analysis also indicated that this model provided the best net clinical benefit. Conclusions Radiomics facilitates a comprehensive exploration of predictors associated with LAA thrombi. A radiomics-based multimodality prediction model can significantly enhance the efficiency of non-invasively detecting thrombi.Receiver operating characteristic curveDecision curve analysis