Although association of human leukocyte antigen (HLA)-DR2 (DRB1*1501) with susceptibility to aplastic anemia (AA) has been well documented in several different ethnic groups, little is known about the protective role of HLA in this disease. HLA-DRB1 alleles were analyzed in 109 Korean AA patients (26 nonsevere and 83 severe) and 800 healthy controls. The frequency of DRB1*1501 was significantly higher in AA patients compared with controls [33.0% vs 15.3%, p=0.000004, p(c)=0.0001, odds ratio (OR)=2.74]. Nonsevere AA (30.8%, OR=2.47) and severe AA patients (33.7%, OR=2.83) showed similar changes, and DRB1*1501 was considered a susceptibility factor to AA in both forms of the disease. The frequency of DRB1*1302 in total AA patients was not different from controls (12.8% vs 17.9%), but it was significantly lower in severe AA compared with nonsevere AA patients (6.0% vs 34.6%, p=0.0006, p(c)=0.02, OR=0.12). DRB1*1302 was considered a protective factor against severe AA. In Koreans, DRB1*1501 was associated with disease susceptibility to AA and DRB1*1302 with protection against the severe form of the disease.