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Objective The aim of this study was to investigate the role of EUS where other investigative techniques had failed to identify the cause of biochemically proven acute pancreatitis. Setting All biliary EUS examinations performed between January 2000 and December 2004 were identified from the radiology computerised database. Patients Forty-two patients (25 male, 17 female; mean age: 53±3.2 years) with negative prior radiological investigations underwent EUS. Main outcome measures Prior and later radiological investigations, hospital readmission, and the need for further surgical intervention were also analysed. Results EUS was normal in 17 patients (40.5%) and demonstrated signs of recent acute pancreatitis but no other aetiological factor in 8 patients (19.0%). Cholelithiasis or microlithiasis was identified in 9 patients (21.4%), combined gallstones/microlithiasis and choledocholithiasis in was seen in 6 patients (14.3%). In one patient (2.4%), calculi were seen in the common bile duct but not the gallbladder. In a further case with recurrent acute pancreatitis (2.4%), chronic pancreatitis was diagnosed on EUS. All patients with common bile duct stones underwent ERCP and sphincterotomy, and stones were universally confirmed. One patient with gallbladder calculi alone required an ERCP after developing jaundice whilst awaiting cholecystectomy. Conclusions EUS provided additional diagnostic information in 17 of the 42 patients (40.5%). Moreover, exclusion of gallstones/microlithiais is also important as it facilitates a search for other causes of pancreatitis. In conclusion, most cases of cholelithiasis can be diagnosed with standard imaging modalities but when these fail to identify a cause, EUS has an important role to play.