Background. Syphilis has reemerged in many vulnerable groups around the world. The objective of the current study was to determine the prevalence and incidence of syphilis among people who attended a specialized HIV clinic in Mexico from 2011-2015.Methods. Databases from the laboratory were analyzed and four groups were formed: people seeking HIV-1 voluntary counseling and testing (VCT), people in prison (PPr), people living with HIV (PLWH) and patients from primary care clinics (others). Syphilis diagnosis was made using the reverse algorithm; antibody titers were examined to determine the stage of infection. Baseline data was analyzed, and with follow-up information, a retrospective dynamic cohort was formed. Factors associated with seroprevalence of syphilis and active syphilis were evaluated by the chi-square test. Moreover, risk factors for the incidence of syphilis were described. Results. A total of 81,863 baseline individuals were analyzed. Syphilis seroprevalence was 9.9% in VCT, 8.2% in PPr, 37.0% in PLWH, and 8.7% in others; the prevalence of active syphilis was 1.7-13.1%. A total of 11,124 people were followed-up; the incidence (cases per 100 years people) was 3.5 among VCT and 16.0 among PLWH; moreover, the frequency of re-infections was 11.1-24.4%. Men, transgender, persons between 20-39 years old, and individuals with a history of HIV or hepatitis B had a higher risk of syphilis. Conclusions. Several vulnerable groups have exhibited a reemergence of syphilis, with high prevalence of active syphilis, high incidence, and re-infections. Persons living with HIV had the highest risk.