Population-specific matching probabilities (MP) are a key parameter to assess the benefits of unrelated stem cell donor registries and the need for further donor recruitment efforts. In this study, we describe a general framework for MP estimations of specific and mixed patient populations under consideration of international stem cell donor exchange. Calculations were based on population-specific 4-locus (HLA-A, -B, -C, -DRB1) high-resolution haplotype frequencies (HF) of up to 21 populations. In various scenarios, we calculated several quantities of high practical relevance, including the maximal MP that can be reached by recruiting a fixed number of donors, the corresponding optimal composition by population of new registrants, and the minimal number of donors who need to be recruited to reach a defined MP. Starting at current donor numbers, the largest MP increases due to n = 500,000 additional same-population donors were observed for patients from Bosnia-Herzegovina (+0.25), Greece (+0.21) and Romania (+0.20). Especially small MP increases occurred for European Americans (+0.004), Germans (+0.01) and Hispanic Americans (+0.01). Due to the large Chinese population, the optimal distribution of n = 5,000,000 new donors worldwide included 3.9 million Chinese donors. As a general result of our calculations, we observed a need for same-population donor recruitment in order to increase population-specific MP efficiently. This result was robust despite limitations of our input data, including the use of HF derived from relatively small samples ranging from n = 1028 (Bosnia-Herzegovina) to n = 33,083 (Turkey) individuals. National strategies that neglect domestic donor recruitment should therefore be critically re-assessed, especially if only few donors have been recruited so far.