Lung transplantation (LTx) is a valid therapeutic option for selected ă patients with end-stage lung disease. HLA-E seems to play a major role ă in the immune response to different viral infections and to affect ă transplantation outcome, in Hematopoietic Stem Cell Transplantation, for ă example. Two nonsynonymous alleles, HLA-E*01:01 and HLA-E*01: 03, ă have functional differences, involving relative peptide affinity, cell ă surface expression, and potential lytic activity of NK cells. The aim of ă this retrospective study was to determine the impact of these two ă alleles for LTx recipients on anti-HLA alloimmunization risk, overall ă survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 ă recipients who underwent LTx from 1998 to 2010 in a single ă transplantation center. In univariate analysis, both HLA-E homozygous ă states were associated with impaired overall survival compared to ă heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, ă HLA-E*01:03 allele showed increased CLAD occurrence when compared to ă homozygous HLA-E*01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = ă 0.047). HLA-E allele did not affect pathogen infection or the production ă of de novo DSA. This retrospective study shows an uninvestigated, ă deleterious association of HLA-E alleles with LTx and requires ă verification using a larger cohort.