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. The slope of RPR decline was compared between BPG and doxycycline groups. Demographics were similar between the groups. A linear mixed effects model, accounting for repeated measurements from the same patient over time, showed no statistically significant difference in the rate of decline between the two treatment groups. These findings suggest that doxycycline dispensed directly to patients, despite its need for daily dosing and adherence for 14-28 days, has treatment outcomes comparable to BPG.