Biliary cast syndrome (BCS), the presence of biliary casts and debris causing biliary obstruction, occurs in 4%-18% of orthotopic liver transplant (OLT) recipients. Potential consequences include cholangitis and graft damage or loss. Limited data exist regarding the etiology and outcomes of BCS. The purpose of this study was to evaluate donor and recipient risk factors and determine the impact of BCS. A retrospective review of 355 OLT cases identified 9 BCS patients (2.5%) diagnosed by cholangiography. Twenty-six matched controls were also identified. The warm ischemic time was significantly longer in BCS patients. Other recipient and donor preoperative and intraoperative characteristics, including the donor risk index, revealed no significant differences. Overall patient survival showed a trend toward worse outcomes at 6, 12, and 18 months and end of follow-up in the BCS group. Overall graft survival was also worse in the BCS group at all time periods, with statistical significance demonstrated at 18 months and end of follow-up. The number of therapeutic biliary procedures and hospital readmissions was significantly higher in the BCS group. Twenty-two percent of the BCS patients required repeat OLT versus none of the control patients. In conclusion, BCS is an uncommon complication of OLT. Except for a longer warm ischemic time, recipient and donor factors did not predict the occurrence of BCS. BCS patients showed a significantly worse graft survival, as well as a trend toward worse patient survival. Given the negative impact of BCS on liver transplant outcomes, further studies appear justified. Liver Transpl 14:1466–1472, 2008. © 2008 AASLD.