Objective This study was performed to assess the diagnostic performance of endoscopic ultrasonography (EUS) in patients with extrahepatic bile duct (EBD) dilatation and develop a novel model incorporating EUS-based signature with clinical parameters for distinguishing the malignant dilation of EBD. Methods The EUS data and clinical parameters of the patients were collected and analyzed retrospectively. First, we evaluated the diagnostic performance of EUS in detecting the cause of EBD dilatation. Then, we performed univariate and multivariate binary logistic regression analyses based on clinical and EUS features. Finally, a nomogram was established to aid in distinguishing between malignant dilation and noncalculous benign dilatation of EBD in patients.Results A total of 184 patients were enrolled. For the diagnosis of malignant dilation, EUS achieved an accuracy of 90.76%, sensitivity of 85.96%, and specificity of 92.91%. For the diagnosis of calculous dilation, EUS achieved an accuracy of 100%, sensitivity of 100%, and specificity of 100%. For the diagnosis of noncalculous benign dilatation, EUS achieved an accuracy of 90.76%, sensitivity of 90.90%, and specificity of 90.58%. Multivariable logistic regression analyses indicated that abnormal liver function test, elevated tumor markers, and EUS findings were the well-diagnostic factors of malignant EBD dilation. The nomogram established by these factors showed good calibration and discrimination. Conclusion EUS is a useful examinational modality in the work-up of EBD dilatation. In combination with abnormal liver function test and elevated tumor markers, EUS may provide additional information for the detection of malignant dilation of EBD and should be further investigated.