Due to a diverse set of complexities, less is known about the pathogenesis of acquired syphilis than most equivalently common pathogens. Among the most clinically and epidemiologically germane of the unanswered questions about the disease is that pertaining to syphilis’ outcomes: which host characteristics are associated with resolution after early-stage infection (which carries little mortality and morbidity risk), vs. persistence into late-stage infection, (which causes significant morbidity)? Our larger project circumvents some of the limitations that have hindered previous studies of syphilis by assessing susceptibility to late-stage syphilis relative to evidence of chronic or episodic stress responses over the life course, age, immune and nutritional status, and comorbidity in adult skeletal individuals with antemortem diagnoses of syphilis in pre-antibiotic era U.S. collections. Here, we present preliminary findings showing associations between early life stress (e.g., linear enamel hypoplasia) and chronic oral infection (i.e., periodontal disease) amongst individuals from U.S. collections as well as from the archaeological record of post-medieval London. In the future, through the use of translation, we aim to use these findings to refine diagnostic and prognostic criteria for syphilis in living people. Rapid increases in syphilis’ global incidence, such as an 80% increase in syphilis cases over the past five years in the U.S., make such advances critical. This bioarchaeological project can therefore fill a crucial gap in understanding the disease ecology of syphilis in ways that can benefit the living.