Hepatitis C virus (HCV) infection is the leading cause of liver transplantation (LT) in Western countries. Polymorphism in the IL28B gene region has a major impact on the natural history and response to antiviral treatment in HCV. We investigated whether IL28B polymorphism was associated with graft survival in patients with or without HCV undergoing LT. 1,060 adult patients (age >18 years) underwent LT between years 2000 and 2008. Patients with previous LT, living donor LT and patients dying or requiring retransplants within 30 days of LT were excluded. DNA samples of 620 (84%) recipients and 377 (51%) donors were available for genotyping of IL28B rs12979860C>T. Donor IL28B genotypes had no significant differences in graft survival irrespective of HCV status. There was no difference in graft outcome in the non-HCV cohort (n = 293) based on recipient IL28B genotype. In the HCV group (n = 327), recipients with CC or CT genotype had better graft survival compared to TT genotype (62% vs. 48%, p = 0.02). HCV recipients with CC or CT genotype had delayed time to clinically relevant HCV recurrence compared to TT (10.4 vs. 6.7 months, p = 0.002). The beneficial effect of the CC/CT genotype on HCV recurrence and graft survival was independent of antiviral treatment. In conclusion, our study demonstrated that in contrast to donor IL28B genotype recipient IL28B was associated with graft survival and clinically relevant HCV recurrence in HCV infected recipients. No effect of IL28B genotype was manifest in non-HCV LT recipients.