The aim of this study was to examine the importance of the serum hepatitis C viral load within the first year post–liver transplant in determining posttransplant survival. A retrospective analysis of 118 consecutive hepatitis C virus–positive liver transplant recipients who received an allograft from January 1997 to September 2005 was undertaken with a median duration of follow-up of 32.4 months. Univariate and multivariate analyses were used to examine the effects of recipient, donor, surgical, and viral factors on posttransplant outcomes. A total of 620 viral load estimations were undertaken in the first 12 months following transplantation. Patient and graft survival rates at 1, 3, and 5 years were 87.8%, 79.9%, and 70.1% and 87.0%, 79.2%, and 68.2%, respectively. According to multivariate analysis, a peak viral load ≥ 107 IU/mL (P = 0.004; hazard ratio, 8.68; 95% confidence interval, 2.04–37.02) and exposure to antirejection therapy (P = 0.05; hazard ratio, 2.26; 95% confidence interval, 1.01–5.38) were both independent predictors of diminished patient and graft survival and hepatitis C–related allograft failure. The only other independent predictor of hepatitis C virus–related outcome after transplant was azathioprine use, which was associated with improved outcomes (P = 0.04; hazard ratio, 0.25; 95% confidence interval, 0.07–0.91). A peak viral load in the first year after transplant of >108, 107 to 108, and <107 IU/mL was associated with a mean survival of 11.8, 70.6, and 89.1 months respectively (P ≤ 0.03). The results emphasize the importance of high viral loads in the early posttransplant period as an independent predictor of recipient outcomes. Liver Transpl 15:709–718, 2009. © 2009 AASLD.