Objective: This study aimed to investigate the association between HLA class II alleles and the occurrence of FVIII inhibitor in Thai hemophilia A patients. Material and Methods: The distribution of HLA-DRB1 alleles and DQB1 alleles in 57 Thai hemophilia A patients and 36 blood donors as controls was determined using the PCR sequence-specific primer (PCR-SSP) method, and the association between the occurrence of factor VIII (FVIII) inhibitor and the presence of certain HLA class II alleles was investigated. Results: The frequency of HLA-DRB1z.ast;15 was higher in the hemophilia A patients with and without FVIII inhibitor, whereas that of DRB1z.ast;14, DRB1z.ast;07, and DQB1z.ast;02 was lower in the hemophilia A patients with FVIII inhibitor, as compared to controls. Interestingly, only the frequency of DRB1z.ast;15 was significantly higher in the patients with inhibitor than in the controls (P = 0.021). Moreover, the frequency of DRB1z.ast;15 in the patients with inhibitor was higher than in those without inhibitor (P = 0.198). Conclusion: The study's findings show that the DRB1z.ast;15 allele might have contributed to the occurrence of inhibitor in the Thai hemophilia A patients; however, additional research using larger samples and high-resolution DRB1 typing is warranted.