Background: Vegetative transjugular intrahepatic portosystemic shunt (TIPS) infections are a rare complication of TIPS placement. Cases have been reported in the literature and one study estimated incidence to be 1%.1 The vast majority of cases were reported in the setting of cirrhosis. Here, we report a case of vegetative polymicrobial TIPS infection refractory to broad spectrum antibiotics in a patient with a prior hepaticojejunostomy anastomosis as part of a Whipple procedure for a pancreatic neuroendocrine tumor. Case Presentation: A 40-year-old gentleman with pancreatic neuroendocrine tumor underwent neoadjuvant chemoradiation therapy and became eligible for tumor resection. A pancreaticoduodenectomy (Whipple resection) with en bloc superior mesenteric vein (SMV) and portal vein-splenic vein confluence resection was performed. The patient developed SMV stenosis, and a TIPS was placed to access the SMV for stent placement. The patient eventually developed recurrent fevers because of Escherichia coli and Enterococcal bacteremia that did not resolve with extended courses of various antibiotics, including meropenem, vancomycin, daptomycin, ertapenem, caspofungin, and piperacillin-tazobactam. The TIPS was eventually removed with an interventional radiology procedure; however, the patient ultimately succumbed to sepsis from antibiotic-resistant bacteria. Conclusion: Here we present a case of endotipsitis in a patient with a biliary enteric anastomosis who did not respond to antibiotic therapy. We caution the use of TIPS in patients with this anatomy, as the biliary tree is inevitably colonized with enteric bacteria and in contact with the intraparenchymal hardware of the TIPS.