Transfusion-related acute lung injury (TRALI) is a rare but serious adverse transfusion reaction and is known to be related to anti-human leukocyte antigen (HLA) or anti-human neutrophil antigen (HNA) antibodies in donor plasma. In 2016, four of eight reported TRALI cases could not be explained by donor antibodies. It is assumed that fewer than 10% of TRALI cases are triggered by anti-HLA or anti-HNA antibodies in the patient's plasma (reverse TRALI). Three cases of red blood cell (RBC)-associated and one case of granulocyte-associated TRALI were investigated. Data were collected on the clinical aspects of the patient and the concerned blood product. Patient's HLA antibodies were determined and the implicated donor was contacted for HLA typing. The HLA antibody identification and strength were assessed using a bead assay (Luminex Single Antigen bead assay, Immucor). For HLA typing, a polymerase chain reaction-sequence-specific oligonucleotide method was used that also included Luminex detection. In three RBC-associated TRALI cases, HLA Class I and II antibodies found in the patient's plasma were specific for the HLA type of the transfused leukoreduced blood product. In a fourth case, HLA antibodies were found in a patient who developed TRALI after repeated granulocyte infusions. The HLA antibodies were directed against HLA antigens present on the donor WBCs. The diagnosis of reverse TRALI was retained in four cases, suggesting that reverse TRALI is more frequent than described in the literature, especially in patients with an increased risk for having HLA antibodies. © 2019 AABB.