Primary non-function (PNF) after liver transplantation has been found to be the most common cause of early graft loss, which accounts for up to 36% of such failures. The cause of PNF is not known. The purpose of this study was to identify factors associated with and independently predictive of PNF after liver transplantation. Four hundreds twenty-four liver transplants performed at the Charles O. Strickler Transplant Center, University of Virginia were retrospectively reviewed. PNF was defined as the failure of an allograft after revascularization with no discernable cause, leading either to retransplantation or to patient death. Risk factors were analyzed using the Pearson chi-square test for univariate analysis and logistic regression for multivariate analysis. Factors found to be associated with PNF included: female recipient (6.4% vs. 2.6%, p=0.045), African-American donor (9.5% vs. 3.2%, p=0.043), inter-racial donor to recipient transplantation (9.5% vs. 2.8%, p=0.008), severe encephalopathy pretransplant (11.1% vs. 3.1%, p=0.034), pretransplant recipient PTT > 50 seconds (10.9% vs. 2.8%, p=0.004), portal vein reconstruction with conduit (15.0% vs. 3.5%, p=0.011), and downsizing of graft (22.9% vs. 3.8%, p=0.007). Logistic regression identified the use of donor iliac vein conduit for the portal vein reconstruction (p=0.003, odds ratio=3.15, 95% confidence interval: 1.49-6.64) and the racial difference between donor and recipient (p=0.012, odds ratio=2.31, 95% confidence interval: 1.20- 4.45) to be independent predictors of PNF. The exact cause of these findings, whether physiologic or immunologic, remains unknown. If confirmed in larger data sets, the attention to these factors may minimize the possibility of PNF in non-emergency situations.