The medical histories of fifty-three consecutive patients who were scheduled for percutaneous transhepatic biliary drainage (PTBD) were reviewed for incidents of sepsis. Among the 52 patients who were successfully catheterized, there were 14 incidents of sepsis, three incidents of abscess and sepsis, and two incidents of sepsis following a pulled catheter (a total incidence of 36.5%). In 14 instances, the sepsis was attributed primarily to the presence of enteric bacteria combined with bile stasis caused by multiple duct obstruction from disseminated malignancy. The presence of bacteria in the bile of well-drained patients did not necessarily lead to sepsis. This series highlights the importance of medical alert for signs of sepsis in biliary drainage patients and suggests that external drainage is preferable in patients with incomplete emptying of the biliary system during PTBD.