Limited evidence suggests that doxycycline may be comparable to penicillin for the treatment of syphilis, but perhaps less so for latent stages. A total of 655 individuals were included, 539 who were treated with benzathine PCN G (BPG) and 116 treated with doxycycline. For our primary analysis, we included all RPR titers up to 24 months after treatment for all stages of syphilis treated from April 2022 through September 2023.