© The Author(s) 2020. HIV pre-exposure prophylaxis (PrEP) effectively prevents HIV acquisition among men who have sex with men (MSM), but PrEP uptake has been associated with sexually transmitted infections (STIs). The effect of PrEP on STIs in MSM in the Deep South of the United States is unknown. We performed a retrospective analysis of adult MSM at an American Deep South PrEP clinic to calculate the prevalence and incidence rate of bacterial STIs (chlamydia, gonorrhea, and syphilis) and identify associated risk factors by linking incident STI to patient-reported outcomes; 139 MSM accessed the clinic between 2014 and 2018 with baseline bacterial STI prevalence of 11%. Twenty-six of 81 eligible MSM on PrEP had incident STIs with an incidence rate of 33.1 cases per 100 person-years. Significantly higher proportions of high PrEP adherence, multiple sexual partners, and inconsistent condom use were seen in those with incident STI, and we identified MSM with both high PrEP adherence and multiple sexual partners as being at especially high risk for bacterial STIs (hazard ratio: 7.57, 95% confidence interval: 1.75–32.74). Bacterial STIs are common after initiating PrEP in this clinic, and MSM reporting high PrEP adherence and multiple sexual partners have a significant risk for incident STI. High-risk sexual behaviors persisted after starting PrEP, highlighting the importance of ongoing, intensive sexual health screening and interventions.