Background: Despite reports that associate donor specific antibody (DSA) with rejection after liver transplantation, grafts are still allocated according to blood group (ABO) but not human leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily disceible clinical association between adverse recipient outcome and DSA. Re-transplantation provides a test environment where the presence of preformed DSA is prevalent and its effect on outcome should be apparent. Methods: All patients undergoing a second liver transplantation with available pre-operative serum were included with the exception of ABO incompatible or multiple organ transplants. Banked sera were tested for anti-HLA antibodies with Luminex-based solid phase assays. Anti-HLA antibodies to the second donor (D2SA) were determined using antibodies specificity and HLA typing of 2nd liver donor. Results: Preformed HLA antibodies directed to second liver transplantation (D2SA) were found in 31 (39％) of the 79 patients that were included in the study. Primary and re-transplantation characteristics were similar in both subgroups except first graft survival which was significantly shorter in recipients who are negative for D2SA. Mean survival of the second graft was similar in D2SA+ and D2SA? cohorts [8.55 (range, 0.01–24.74) vs. 7.56 (range, 0–23.53) years respectively, P=0.574]. Mean patient survival after 2nd liver transplantation was similar in D2SA+ and D2SA? cohorts [9.11 (range, 0.01–24.74) vs. 8.10 (range, 0–23.53) years respectively, P=0.504]. Subgroup univariate analysis demonstrated no detrimental effect of class, locus, or strength of D2SA on survival of the second liver transplant. In multivariate cox regression model, neither class I D2DSA (HR =1.101, P=0.92) nor class II D2SA (HR =1.74, P=0.359) were significant risks of graft failure. Conclusions: Presence of D2SA was not found to be associated with inferior outcomes in this retrospective cohort study of liver re-transplantation suggesting that changes to the allocation system are not required.