Abstract: CONTEXT: Transfusion-related acute lung injury (TRALI) which is associated with passive transfer of antibodies to leukocyte antigens in blood products causes serious morbidity and mortality. Blood donation centers need to determine the best measure to mitigate the risk of TRALI. AIM: This study was conducted to evaluate the characteristics of blood donors implicated in TRALI cases and donors who were found to have human leukocyte antigen (HLA) antibodies. SETTING AND DESIGN: This was a cross-sectional study based on a retrospective record review in the Histocompatibility and Immunogenetics Laboratory, National Blood Centre, Kuala Lumpur. SUBJECTS AND METHODS: All cases investigated for TRALI from January 2017 to February 2022 were included. Donor’s variables analyzed include age, gender, race, history of alloimmunization, and result of HLA antibody test. Corresponding HLA antigen in recipient, recipient outcome and implicated blood product were also studied. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS version 22. RESULTS: Twenty-seven cases of TRALI with 37 donors were investigated. Majority of the donors were female (73%). Packed red cell was the most frequently implicated blood product (70.3%). There were significant associations between gender (P = 0.029) and history of pregnancy (P = 0.014) with the presence of HLA antibody in the donors. Multiparous donors with HLA antibodies have a higher number of pregnancies compared to their counterparts (mean = 3.93 [1.69] vs. 2.20 [0.84]) with a significant difference (P = 0.044). CONCLUSION: The characteristics of blood donors and blood products implicated in TRALI cases and donors who have HLA antibodies were identified. The impact of deferring certain blood donor group needs to be determined before the most appropriate TRALI mitigation strategy can be implemented.