BACKGROUND The development of specific antibodies against human leukocyte antigen (HLA) and/or human platelet antigen (HPA) could induce platelet transfusion refractoriness especially in patients receiving multiple platelet transfusions. A retrospective analysis was conducted to evaluate the prevalence of platelet-specific antibodies and the efficacy of crossmatch-compatible platelet transfusions in these recipients. METHODS All enrolled patients were refractory to random single-donor apheresis Platelet (PLT) units. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-HLA and anti-HPA antibodies in serum. For those patients with antibodies, the PLT crossmatch assays were performed to select the compatible PLTs with a commercial solid-phase adherence kit. RESULTS A total of 193 patients were included and 29.02% of which was HLA and/or HPA antibody-positive. There were no significant differences in antibody-positive rates among AML/CML, ALL/CLL, MDS, SAA and ITP groups, but they are statistically significantly higher than other groups (P = 0.0035). Of those antibody-positive patients, there were 41 (73.21%) patients with only HLA antibodies, 11 (19.64%) patients with only HPA antibodies and 4 (7.14%) patients with both HLA and HPA antibodies. A total of 43 random PLT units and 88 crossmatch-compatible PLT units were administered. The mean (± SD) corrected count increment (CCI) was 8700 (± 4500) after crossmatch-compatible unit transfusion, significantly higher than 3600 (± 2400) for random PLT units (P < 0.001). CONCLUSIONS HLA and/or HPA alloimmunisation is an important factor to cause refractoriness to platelet transfusions. Crossmatch-compatible platelet transfusion is an effective method in those patients refractory to random platelet transfusions.