Diagnosis of sexually transmitted infections is very important considering the spread of HIV and the extensive use of highly active antiretroviral therapy worldwide. This will assist in planning of treatment schedule in controlling these infections. The study therefore aimed at determining the prevalence of syphilis in HIV positive antiretroviral therapy naive patients in Cape Coast and the associated risk factors involved in infection. A cross-sectional study was carried out using initial HIV rapid and confirmation tests, and then Venereal Disease Research Laboratory test with the Ultra Rapid Test Kits for syphilis. Demographic data, risky sexual behaviours capable of co-transmission of both HIV and Syphilis, were also collected through the use of questionnaires. In all, 150 HIV positive antiretroviral naive subjects were studied and 15 (10%) were positive for VDRL test, with females (6.00%) and males (4.00%), who were mainly within the age group of 20-39 years. A significant number of males (p = 0.019) and females (p = 0.015) participants were not smoking with a fewer number of the females (p = 0.002) having multiple sexual partners. Also a smaller number of those who were infected with the bacteria (p = 0.004) did not support the control of sexually transmitted infection (p = 0.022). The result showed that co-infection of Syphilis in HIV positive antiretroviral therapy naive patients persists in the Cape Coast Metropolis, which is an indication of prominence of STIs that require further study on a larger scale to ascertain the extent of co-infection and to formulate policy for treatment to help minimize the rate of infection.