Identifying candidates for HIV pre-exposure prophylaxis (PrEP) is a barrier to improving PrEP uptake in priority populations. Syphilis infection is an indication for PrEP in all individuals and can be easily assessed by primary care providers (PCP) and health systems. This retrospective study evaluated the impact of a multidisciplinary provider outreach intervention on PrEP uptake in patients with a positive syphilis test result in a safety-net hospital-based primary care practice. The PCPs of PrEP-eligible patients with a positive syphilis result were notified via the electronic medical record (EMR) about potential PrEP eligibility and institutional HIV PrEP resources. Rates of PrEP offers and prescriptions were compared in the pre (8/1/2018-12/31/2018,  = 60) and post (1/1/2019-5/31/2019,  = 86) intervention periods. Secondary analyzes evaluated receipt of appropriate syphilis treatment and contemporaneous screening for HIV, gonorrhea, and chlamydia. No significant differences in the overall proportion of patients offered (15% vs 19%) and prescribed (7% vs 5%) PrEP were observed between the pre- and post-periods. Overall, 7% of positive tests represented infectious syphilis. The rate of appropriate syphilis treatment was equivalent (57% vs 56%) and contemporaneous screening for other sexually transmitted infections was suboptimal across the entire study period. Although any positive syphilis test may be an easily abstracted metric from the EMR, this approach was inclusive of many patients without current HIV risk and did not increase PrEP uptake significantly. Future research into population health approaches to increase HIV prevention should focus on patients with infectious syphilis and other current risk factors for incident HIV infection.