Objective To evaluate diagnostic efficacy of endoscopic ultrasonography (EUS) for extra-hepatic bile duct dilation of unknown reasons which failed to be identified by traditional radiological methods. Methods Data of consecutive 892 patients who underwent EUS from February 2016 to September 2017 were retrospectively studied. Final diagnosis was determined by endoscopic retrograde cholangiopancreatography (ERCP)-based biopsy, surgical pathology, or a follow-up of at least 10 months. Results A total of 82 patients with extra-hepatic bile duct dilation (width ≥ 7 mm) and mean age of 61.5±9.6 years were included. The width of common bile duct was 13.0±4.25 mm. Reasons for extra-hepatic bile duct dilation could be determined by EUS in most patients with abnormal liver function. No malignant causes were detected in patients with normal liver function. The diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value of EUS were 92.7%, 100.0%, 96.3%, 100.0%, and 93.2%, respectively. Conclusion For patients with dilated extra-hepatic bile duct without clear etiology, EUS may be an alternative for determining the etiology of extra-hepatic bile duct dilation. For those with extra-hepatic bile duct dilation with abnormal liver function, malignant causes should not be neglected.