Background In recent years, the number of cases of syphilis has been increasing at both local and global levels. In this study, we sought to profile how this increase in cases has translated to the inpatient setting by examining inpatient admissions due to or complicated by syphilis at any stage. Methods At a single-center, multisite health institution, charts for patients older than 18 years admitted between April 2017 and October 2020 with a diagnosis of syphilis were reviewed. Cases were characterized into stages of primary, secondary, latent, tertiary, and neuro/ocular syphilis, with all neuro/ocular cases categorized together despite the potential for neuro/ocular syphilis at any stage. Medical history, laboratory data, hospital course, and treatment outcomes were recorded. Results Eighty-one charts met inclusion, with a mean age of 49 years. Seventy-two percent were cisgender men, 42% were documented as men who have sex with men, and 49% were of Black race. Thirty-three percent had been previously diagnosed with syphilis, and 70% of that group had previously received treatment. Forty-one percent were HIV+. Fifty-one percent were cases of neurosyphilis, and 42% were latent. The mean LOS was 10 days, with 11% readmitted within 30 days. Conclusions These results formulate a profile for the outlook and course of hospitalizations for or complicated by syphilis in an urban setting. In light of these findings, and given the rising incidence of syphilis in the world, opportunities for further investigation into prevention, impact, and outcome quality are more necessary than ever.