We analyzed the association of HLA antigens with incidence of organ-specific graft-versus-host disease (GVHD) after allogeneic hemopoietic stem cell transplantation (allo-HSCT) from an HLA-matched sibling donor. We retrospectively reviewed the clinical records of allo-HSCT recipients and found 389 patients who had received matched-sibling HSCT. HLA types, GVHD grades, and the development of acute or chronic GVHD, factors that reflect a certain immunological impact associated with involved organs, were investigated. The overall incidence of acute and chronic GVHD was 24.8% (96 cases) and 21.2% (82 cases), respectively. The incidence of acute GVHD with grades II through IV was higher among patients who had HLA-B61 (P = .0153) and HLA-Cw3 (P = .0208). The donor sex (P = .0040) and the conditioning regimen (P = .0010) were also associated with severe acute GVHD. The extensive-type chronic GVHD incidence was higher in patients who had HLA-B54 (P = .0159). The donor sex (P = .0406) and the pretransplantation diagnosis (P = .0184) were other factors associated with the development of extensive-type chronic GVHD. Furthermore, HLA-B35 (P = .0226) and HLA-B54 (P = .0091) were associated with a higher incidence of severe acute skin GVHD and chronic skin and oral GVHD (in descending order of incidence rates). HLA-B7,27 was associated with chronic liver GVHD (P = .0476) in addition to other parameters including patient (P = .0246) and donor sex (P = .0019). This study shows that these remarkable HLA antigens may be potent transplantation immune regulators, but there is a need for further evaluation using larger study samples.