Intraductal papillary mucinous neoplasm (IPMN) of the main pancreatic duct is usually treated by surgical excision of the affected pancreas. Nonoperative ablative therapies have not been described. We treated IPMN of the pancreatic duct with photodynamic therapy (PDT) in a patient who was a poor operative candidate. Porfimer sodium was administered intravenously, and laser light was delivered by a diffusing catheter placed in the pancreatic duct during endoscopic retrograde cholangiopancreatography (ERCP). Imaging and biopsy findings of IPMN resolved after PDT, and symptoms also resolved. Metastatic cancer was diagnosed 2 years after PDT had been initiated. Pancreatic PDT was well tolerated in this case, and may be a therapeutic option for selected patients with IPMN of the main pancreatic duct.