Background and Aim: Although the role of intraductal ultrasound (IDUS) in the evaluation of specific disease entities is well known, its utility in evaluating indeterminate findings in a heterogeneous group of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) is unknown. This study evaluates the diagnostic accuracy of IDUS in patients with indeterminate findings at ERCP. Methods: This was a prospective study of all patients who underwent IDUS for evaluation of an indeterminate biliary stricture or main pancreatic duct (MPD) dilation noted at ERCP over an 8-month period. The accuracy of IDUS was established based on long-term follow-up, surgery, or further investigations. Results: Twenty-nine (5%) of 600 patients who underwent ERCP had an indeterminate finding that warranted further evaluation by IDUS: this was biliary stricture in 19 patients and MPD dilation in 10. Technical success was 100%. Mean duration of follow-up was 435 days (range 192-614 days). In patients with biliary stricture, IDUS diagnosed 11 as benign and eight as malignant. In patients with MPD dilation, IDUS diagnosed intraductal papillary mucinous tumor in six patients and chronic pancreatitis in four. Findings on IDUS supported the correct diagnosis in 27 of 29 patients (93%). In two patients with dominant hilar stricture in the setting of primary sclerosing cholangitis, IDUS was false positive in one and false negative in the other. One patient died of multiorgan failure due to post-ERCP pancreatitis. Conclusions: A technically easy procedure, IDUS offers unique advantages in the evaluation of patients with indeterminate findings at ERCP. © 2007 The Authors.