Background: 10–30% of patients with pancreatitis are classified as idiopathic after the initial evaluation. Our aim was to assess the diagnostic yield of endoscopic retrograde cholangiopancreatography (ERCP) and sphincter of Oddi manometry in patients with idiopathic pancreatitis in a tertiary referral center. Methods: A single-center, retrospective study analyzing the ERCP and manometry results of 1,241 patients who were classified as having idiopathic pancreatitis based upon their initial evaluation. Results: A single episode of pancreatitis occurred in 20.4%, acute recurrent pancreatitis in 56.3% and chronic pancreatitis in 23.3% of the patients undergoing ERCP. Sphincter of Oddi dysfunction was found in 40.3% and pancreas divisum in 18.8% of the patients. Biliary stone disease was found in 3.0%. Intraductal papillary mucinous neoplasms were identified in 52 patients with increasing frequency in older age groups. The overall diagnostic yield of ERCP and sphincter of Oddi manometry to elucidate a potential cause of pancreatitis was 65.8%. Of these, 91.9% patients had findings amenable to endoscopic therapy. The complication rate was 11.5%. Conclusions: In this large series, ERCP with manometry frequently identified conditions which probably caused or contributed to the idiopathic pancreatitis. Long-term studies are awaited to determine outcomes after correctable factors are addressed.

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