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Pancreas divisum (PD), the most common congenital anatomic variation of the pancreatic ductal system, is still rare in clinical practice. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for patients with symptomatic PD. However, even by experienced endoscopists, the procedure of ERCP can fail in 3% to 10% of cases. Traditionally, if we fail in cannulation we have no choice but to rely on surgery.The 2 case reports of PD in this study with cannulation were both unsuccessful, fortunately, the use of endoscopic ultrasonography–guided pancreatic duct puncture combined with ERCP was eventually successful in treatment.Using endoscopic ultrasonography–guided pancreatic duct puncture combined with ERCP is safe and effective for the treatment of the patients of difficult minor papilla cannulation in patients of PD, and can be used as a remedy for minor papilla cannulation failure.