Objective: The objective of this study was to describe the prevalence of sexually transmitted co-infections and assess factors associated with a single infection and co-infections. Methods: A total of 388 women were included in this study. At enrollment of the EVRI trial women were tested for five STIs: Human papilloma virus (HPV), Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus-2 (HSV-2) and Treponema pallidum. Prevalence of STI infections and proportion of women with different combinations of co-infections were calculated. Factors associated with single infection and STI co-infection were assessed using a polytomous logistic regression model and odds ratio (OR) and 95% confidence intervals (95% CI) were reported as the measure of association. Results: Prevalence of a single STI and concurrent STI co-infections were high. Prevalence of chlamydia was 33%, syphilis 6%, HSV-2 46% and HPV 71%. The most common STI co-infection pattern was HPV-HSV (32%), followed by HPV-chlamydia (17%). The odds of single STI compared to no STIs was significantly lower for women who had education level of grade 7 compared to women who had some college or technical education (OR 0.16, 95% CI: 0.03-0.79).The odds of a single STI compared to no STIs were significantly higher (OR 3.02, 95% CI: 1.05-8.64) and the odds of concurrent STIs compared to no infection were significantly higher (OR 3.86, 95% CI: 1.42-10.48) for women with three or more lifetime partners compared to one life time partner. Conclusions: STIs, single and multiple concurrent infections, are common among this cohort of South African women. These results strengthen the recommendation that STI screening and treatment needs to be a component of multiple intervention strategies among high-risk women residing in communities with high STI prevalence.