Platelet transfusion refractoriness (PTR) is the major complication of long-term platelet supportive care. To improve the effectiveness of platelet transfusion therapy in PTR patients, we aimed to establish a platelet donor registry in our region (Guangzhou, China) by typing the human leukocyte antigen (HLA) and human platelet antigen (HPA). Blood donors (n = 864) from our population were genotyped for HLA-A, HLA-B and HPA systems by polymerase chain reaction amplification with sequence-specific primer(PCR-SSP) techniques. Using this cohort, we compared the results of platelet transfusions (matched vs. random) in 23 patients with PTR. Matched platelets were selected either by HLA antigen matching or by HLA antibody matching, as predicted by antibody specificity prediction (ASP) analysis. Significantly higher platelet recovery (PPR) values were obtained with HLA-matched platelets in comparison with random platelets. No significant difference in PPR was observed between HLA matching and ASP methods. In two patients, platelet-specific alloantibodies (alloabs) (anti-HPA-3b and anti-HPA-5b) were detected besides HLA class I alloabs. Transfusion with HLA- and HPA-compatible platelets in both the patients resulted in significantly higher PPR when compared with HLA-compatible platelet transfusion alone. In this study, we demonstrated that the establishment of an HLA- and HPA-typed platelet aphaeresis donor registry is useful to improve the treatment outcome of PTR patients and to maintain a long-term platelet transfusion strategy.