We investigated an association of human leukocyte antigen (HLA)-DR13 to graft survival in liver transplantation among Caucasian recipients. 28,708 deceased liver transplants performed between January 1990 and December 2002 in the United States as reported to the United Network for Organ Sharing registry were utilized to compare survival rates. We utilized Caucasian adult patients (>20 years) by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard analyses. HLA-DR13-negative hepatitis B virus (HBV) and primary sclerosing cholangitis (PSC) recipients yielded significantly lower graft survival rates than those of DR13-negative patients (P = 0.002, P = 0.015, respectively). This negative association was still significant after adjusting potential confounding factors. The Cox test demonstrated that HLA-DR13-positive groups have a significantly higher hazard ratio in PSC (1.40; P = 0.029; 95% confidence interval, 1.04-1.90) and HBV patients (1.78; P = 0.032; 95% confidence interval, 1.05-3.02). In conclusion, our data suggest that HLA-DR13 is a strong, positive predictor of increased risk for graft loss in HBV and PSC liver transplant recipients. Further study is needed to test the hypothesis that DR13-related immune responses may play a role in mediating graft loss in HBV and PSC liver transplantations. Liver Transpl 12:600–604, 2006. © 2006 AASLD.