Introduction: Recent outbreaks of syphilis occurred predominantly in men who have sex with men (MSM). A significant proportion of syphilis cases occur in MSM who had more than one episode of syphilis. This group may play an important role in syphilis transmission. Aim: To identify factors associated with the risk of syphilis reinfection. Material and methods: Forty-four MSM patients with the first episode of syphilis who were treated at the Department of Dermatology at the Jagiellonian University School of Medicine in Krakow, Poland were included in this study. After completing the treatment, the RPR testing was done every 3 months for 2 years in every patient. In the study period, we identified 12 (22%) cases of syphilis reinfection, eight of which were asymptomatic. Clinical, demographic and behavior data from patients with only one episode of syphilis were compared with those collected from repeaters. Results: Individuals with syphilis reinfection had concomitant HIV infection more frequently, reported a higher number of sexual partners and had sex in sex on premises venues more frequently (p < 0.05). In the multivariate analysis, we found that being HIV-infected MSM and having sex in sex on premises venues independently correlated with a higher risk of syphilis reinfection (OR = 9.6, 95% CI: 2.2-42.5 and OR = 5.6, 95% CI: 1.4-22.5, respectively). Conclusions: Results of our study highlight a strong need for frequent and repeated screening among MSM patients (especially those with concomitant HIV infection) with the first episode of syphilis and taking detailed patient’s history regarding also demographic and behavior data. We should also improve prevention policies to reduce risk behaviors in this population.