The purpose of our study was to determine the rate of sepsis and cholangitis associated with percutaneous biliary drain cholangiography and subsequent drain exchanges and to compare the incidence of these complications between patients with liver transplants and those with native livers. A retrospective review of 154 consecutive patients (100 with liver transplants and 54 with native livers) who underwent a total of 910 percutaneous biliary drain cholangiography examinations and exchanges (January 2005 to July 2008) was performed. Cholangitis was defined as fever (> 38.5°C) within 24 hours after the intervention, and sepsis included cholangitis in addition to hemodynamic instability. The overall incidence of cholangitis and sepsis after percutaneous biliary drain exchanges was 2.1% (n = 19/910 exchanges) and 0.4% (n = 4/910 exchanges), respectively. There was no statistically significant difference in complications between liver transplant patients versus nontransplant patients (p = 0.34 for cholangitis and p = 1.00 for sepsis). The mean hospital stay due to postprocedural complications was 2.4 days for observation and supportive treatment. None of these patients required an intensive care stay. Mean percutaneous biliary drain dwell time in liver transplant and nontransplant patients was 6.2 and 1.5 months, respectively. Transplant patients were significantly younger (54 versus 67 years; p << 0.05), male predominant (70% vs 52%, p = 0.035), and had more severe liver disease (12.2 vs 8.0 Model for End-Stage Liver Disease [MELD] scores; p << 0.05). Percutaneous biliary drain cholangiography and exchange is associated with a low rate of postprocedure cholangitis and sepsis. These complications require brief hospitalizations. Liver transplant patients do not have an increased risk of complications despite higher MELD scores and longer intubation periods.