End-stage renal disease (ESRD) is a significant public health issue with an estimated increasing burden over the next 10 years. Early prediction of patients with a high risk of ESRD progression is crucial to monitor and initiate appropriate interventions, of which HLA alleles have been proposed as promising biomarkers. This cross-sectional study described HLA profiles of a Vietnamese cohort and investigated the association between HLA alleles and ESRD. All ESRD patients who were waitlisted to receive kidney transplant and potential donors in a tertiary hospital from March 2018 to April 2020 were invited to participate in the study. A total of 458 participants were eligible, including 126 ESRD patients and 126 family-related donors, 98 ESRD patients and 108 unrelated donors. HLA typing was performed using Luminex-based PCR-SSO technology. We found HLA-A*02, A*11, A*24, B*15, B*07, DRB1*12, DRB1*09, DQA1*01, DQA1*06, DQB1*03 and DQB1*05 as the most common alleles, which is similar to the general Vietnamese population and other countries in East and South-east Asia. HLA-B*07 (P = .040), DQA1*06 (P = .031), and DQB1*03 (P = .036) were susceptible to ESRD, while HLA-B*27 (P = .024) and DQB1*02 (P = .006) were associated with a decreased risk of ESRD.