Transfusion-related acute lung injury (TRALI) is a non-hemolytic adverse reaction that occurs ≤6 hours after receiving a transfusion. A 72-year-old man with leukemia developed severe hypoxemia after platelet transfusions on two occasions within a 4-day period. During the first episode, the transfused platelet preparation was positive for anti-human-leukocyte antigen antibodies. The pathogenesis of TRALI includes an antibody-mediated mechanism and a non-antibody-mediated mechanism, in which various factors combine to activate pulmonary neutrophils. In our case, it is considered that the patient's neutrophils reached the activation threshold for the development of TRALI after the accumulation of various factors besides anti-leukocyte antibodies.