Hematogenous prosthetic joint infections (PJIs) are primarily associated with Staphylococcus aureus, and there is a 30%-40% risk of contracting a hematogenous PJI following an S. aureus bacteremia. The aim of this study was to investigate whether identical strains of S. aureus were present in each patient from a cohort with both bacteremia and PJI and to explore the genomic differences between paired isolates obtained from blood cultures and tissue biopsies. All patients with a PJI and a temporally concomitant bacteremia due to S. aureus from 2005 to 2020 were included. Paired isolates of S. aureus from tissue biopsies and blood cultures were subjected to whole-genome sequencing. Twenty-four episodes of PJI were identified in 23 patients. All pairwise isolates from individual patients belonged to the same multilocus sequence type, clonal complex, and core genome multilocus sequence typing (cgMLST) complex type. The median number of single nucleotide polymorphisms (SNPs) in the conserved core genomes between the pairwise isolates was 3. In conclusion, identical cgMLST complex types and low levels of SNP differences between paired isolates of S. aureus from blood cultures and tissue biopsies suggest hematogenous seeding in all cases of PJI in this cohort.