Haematopoietic stem cell transplantation (HSCT), using unrelated donors (UD), is now a common modality of treatment for individuals with a variety of different diseases. HLA matching has been shown to have a significant impact on patient outcome. This study includes 423 unrelated UK patient/donor pairs. The patients and donors were typed at high resolution for HLA-A, -B, -C, -DRB1, -DQB1, -DPB1. The degree and type of HLA mismatch was found to be a significant factor affecting outcome. The matching status for DPB1, both at an allele and epitope level, significantly affected transplant complications. The findings of this study have made it possible to offer advice concerning the choice of the most appropriate unrelated donor to select in order to achieve the best patient outcomes.