A 44-year-old gentleman with stage III (T4N1M0) unresectable pancreatic adenocarcinoma at the uncinate process underwent percutaneous image guided Irreversible Electroporation (IRE). At day-1 post IRE the patient developed severe abdominal pain and had computed tomography for assessment of his symptoms. Computed tomography showed severe duodenal wall thickening with local inflammatory changes and was reported as duodenal infarction based on imaging features. Following conservative management with better pain management, both the clinical symptoms and imaging features resolved uneventfully. This case has highlighted severe duodenal swelling seen in patients post IRE for locally advanced pancreatic cancer may mimic duodenal infarction and is an important differential diagnosis to ensure appropriate clinical management.