<h3>Background</h3> The public health impact of syphilis worldwide underscores the need to develop an effective vaccine. We established a global consortium for syphilis vaccine development, and collected Treponema pallidum (Tp) DNA from well-characterized syphilis patients for whole genome and outer membrane protein (OMP) sequencing. <h3>Methods</h3> Patients with primary, secondary or early latent syphilis were enrolled from four sites located in Chapel Hill (United States), Cali (Colombia), Lilongwe (Malawi) and Guangzhou (China) beginning November 2019. Inclusion criteria included age ≥18; early syphilis based on symptoms/signs, sexual history; positive darkfield microscopy, nontreponemal and treponemal antibodies. Patient demographics, clinical presentation, syphilis staging, HIV co-infection, and nontreponemal antibody titers were recorded. Ulcer swabs and skin biopsies were collected for DNA extraction, and blood was obtained for rabbit infectivity testing (Guangzhou site). Tp burdens in specimens were quantitated by qPCR for polA (tp01021). <h3>Results</h3> To date, 833 patients have been screened and 94 enrolled across all sites (median age of 27, range: 18–59). Among enrolled participants, 31% are female, 22% are men who have sex with men, and 20% are HIV-coinfected. Primary syphilis was confirmed in 43 persons by darkfield microscopy, and all syphilis cases were confirmed by serology. Nontreponemal titers ranged from 1:1–1:256. Twenty-one Tp strains have been isolated from rabbits, building upon recently published genomes. Tp qPCR assays have been performed on 79 specimens so far, providing a range of copy numbers based on specimen type and stage. Twenty specimens have been sequenced to-date, and analysis for structural variability in OMP targets is underway. <h3>Conclusion</h3> We established a global clinical research consortium and have begun to characterize Tp genomic sequences and catalog Tp's global repertoire of OMPs based on strains circulating in affected populations across sites. Our findings will enable us to identify vaccinogens with broad protective capacity against circulating Tp strains.