ABSTRACTCampylobacter ureolyticusis an emerging pathogen increasingly appreciated as a common cause of gastroenteritis and extra-intestinal infections in humans. Outside the setting of gastroenteritis, little work has been done to describe the genomic content and relatedness of the species, especially regarding clinical isolates. We reviewed the epidemiology of clinicalC. ureolyticuscultured by our institution over the past 10 years. Fifty-one uniqueC. ureolyticusisolates were identified between January 2010 and August 2022, mostly originating from abscesses and blood cultures. To clarify the taxonomic relationships between isolates and to attribute specific genes with different clinical manifestations, we sequenced 19 available isolates from a variety of clinical specimen types and conducted a pangenomic analysis with publicly availableC. ureolyticusgenomes. Digital DNA:DNA hybridization suggested that theseC. ureolyticuscomprised a species complex of 10 species clusters (SCs) and several subspecies clusters. Although some orthologous genes or gene functions were enriched in isolates found in different SCs and clinical specimens, no association was significant. Nearly a third of the isolates possessed antimicrobial resistance genes, including theermAresistance gene, potentially conferring resistance to macrolides, the treatment of choice for severe human campylobacteriosis. This work effectively doubles the number of publicly availableC. ureolyticusgenomes, provides further clarification of taxonomic relationships within this bacterial complex, and identifies target SCs for future analysis.