In the setting of hematopoietic stem cell transplantation, donor-patient HLA matching is the prime donor selection criterion. Matching algorithms provide ordered lists of donors where the probability of a donor to be an HLA match is calculated in cases where either donor or patient HLA typing information is ambiguous or incomplete. While providing important information for the selection of suitable donors, these algorithms are computationally demanding and often need several minutes up to hours to generate search results. Here, we present a new search kernel implementation for Hap-E Search, the haplotype frequency-based matching algorithm of DKMS. The updated search kernel uses pre-calculated information on donor genotypes to speed up the search process. The new algorithm reliably provides search results in 9 Mio donors) including matching and mismatching donors, even for frequent or incomplete patient HLA data where the matching list contains several thousand donors. In these cases, the search process is accelerated by factors of 10 and more compared to the old Hap-E Search implementation. The predicted matching probabilities of the new algorithm were validated with data from verification typing requests of 67,550 donor-patient pairs.