Trueperella pyogenes, a bacterial opportunistic pathogen residing along the skin layer of apparently healthy animals, is the etiologic agent of intracranial abscessation-suppurative meningoencephalitis, a cause of mortality for male white-tailed deer (Odocoileus virginianus). Occurrence of this disease has been speculated to be influenced by virulence of T. pyogenes residing on white-tailed deer in geographically distinct metapopulations. To determine if differences in virulence potential of T. pyogenes could affect occurrence of disease across populations, we examined if frequency of seven virulence genes of T. pyogenes from forehead swabs of 186 apparently healthy white-tailed deer differed between sites in the state of Georgia, US, where ≥1 male tested positive for a cranial abscess and sites where no individuals tested positive for a cranial abscess. We detected six of seven virulence genes more frequently at sites where we detected ≥1 male with a cranial abscess compared to sites where we did not detect any individuals with a cranial abscess (nanH, P<0.001; nanP, P=0.007; fimA, P<0.001; fimC, P=0.037; fimE, P<0.009; fimG, P<0.001; and cbpA, P=0.872). Our findings suggest differences in the pathogenic potential of T. pyogenes at individual sites may help to explain spatial variability of this disease. Anecdotally, the incidence of cranial abscess disease in Georgia seems to be associated with areas that were restocked with white-tailed deer from a high-fenced property in Wisconsin, US. Given the spatial distribution of this disease, we speculate that these genetic differences in T. pyogenes may have arisen from white-tailed deer restocking efforts, and our observations may be a legacy of an introduced disease manifesting itself generations later.