The characteristics and serological responses of primary syphilis are not completely understood. We aimed to describe the characteristics, the serological responses and presumptive treatment of primary syphilis in HIV-positive and -negative men who have sex with men (MSM). We conducted a retrospective review of microbiological and demographic information from MSM presenting with primary syphilis. There were 111 cases of primary syphilis in MSM, the median age was 46 (IQR = 37–53years) and 40 (36%) were living with HIV. Fifty percent of MSM presented with painful lesions and 14% with extra-genital lesions. Extra-genital lesions were significantly more likely to be painful than non-genital lesions (OR 4.72; 95%CI = 1.25–17.83, p = 0.02). Overall, a reactive serological response demonstrated a sensitivity of 80% (57/71) compared with Treponema pallidum PCR. Serology was more sensitive in MSM with no previous syphilis (OR = 3.38, 95%CI = 1.00–11.43, p < 0.05). MSM presenting with painless lesions were more likely to be treated presumptively (OR = 3.39, 95%CI = 1.38–8.33, p < 0.002). There were no differences in the characteristics, serological responses or management according to HIV status. Fifty percent of MSM with primary syphilis presented with painful lesions; extra-genital lesions are more likely to be painful than genital lesions, serology is positive in 80% and there were no differences between HIV-positive and -negative MSM. Understanding the characteristics of primary syphilis will underpin public health campaigns.