Abstract Human leukocyte antigen (HLA) haplotype frequency distributions in specific populations can be applied to optimize both individual stem cell donor searches and donor registry planning. We present allele and haplotype frequencies derived from a data set of 8862 German stem cell donors who were typed at high resolution for the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genes upon registration. Calculated haplotype frequencies were used to estimate the probability p to find matching donors subject to donor registry size n . The impact of various matching standards on p ( n ) was analyzed. When high-resolution matching for HLA-A, HLA-B, HLA-C, and HLA-DRB1 is required, p (1,000,000) is 0.678. The corresponding value for n = 7,000,000 is 0.859. In a scenario with low-resolution matching and no consideration of HLA-C, p (1,000,000) is 0.863 and thus larger than p (7,000,000) in the scenario with stricter matching requirements. As recent findings support the importance of high-resolution matching of HLA-A, HLA-B, HLA-C, and HLA-DRB1 for outcomes of hematopoietic stem cell transplantation, our results are highly relevant for strategic planning and resource allocation of donor centers and registries.