Sepsis following the placement of a transjugular intrahepatic portosystemic shunt (TIPS) has been reported in up to 10% of cases. This report describes an unusual case of polymicrobial gram-negative sepsis after placement of TIPS associated with a cholangiographically documented fistulous connection between the biliary tree and shunt. The patient was treated with temporary biliary stent placement, endoscopic sphincterotomy, and broad-spectrum antibiotics with rapid closure of the fistula and resolution of sepsis. In the absence of hemobilia, it is hypothesized that flow through the fistula allowed bilious contamination of the systemic circulation and subsequent inoculation with enteric flora. The prevalence of biliary-vascular fistula after placement of TIPS is unknown. It may be a previously unsuspected source of sepsis after placement of TIPS and is likely to be overlooked unless endoscopic retrograde cholangiopancreatography is performed.