Syphilis is a chronic sexually transmitted infection that is caused by the spirochete bacterium Treponema pallidum subsp. pallidum (T pallidum). Although syphilis is mistakenly believed to be a disease of the past, it is actually still endemic in low and middle-income countries, and it has been steadily resurgent in high-income nations, including the USA, for the past 20 years. An effective syphilis vaccine would greatly help curtail syphilis spread. Our current understanding of syphilis pathogenesis suggests that for a syphilis vaccine to be effective, it must induce antibodies able to opsonize antigens on T. pallidum surface to induce pathogen ingestion by macrophages. To this end, we used three T. pallidum putative surface antigens as vaccine candidates, which belong to the T. pallidum repeat (Tpr) protein family, specifically TprC, TprK, and TprD2. Once synthesized as recombinant antigens, New Zealand White (NZW) rabbits were immunized every three weeks with a total of five injections, and then challenged with infectious T. pallidum on their shaved backs. After the challenge, the efficacy of the vaccine candidate was tested by monitoring several correlates of protection, including lesion development and treponemal burden within the injection sites. Immunization with the TprC and TprK antigens induced attenuated lesions and reduced treponema burden, but not immunization with TprD2. Although at the end of the experiment all the rabbits were positive for syphilis infection based on serology, we demonstrated that TprC and TprK were effective in inducing partial protection, and therefore should be considered as vaccine candidates for this serious infection.