Severe inequities in HIV pre-exposure prophylaxis (PrEP) access and use in communities hardest hit by the HIV epidemic persist, further exacerbating ongoing racial/ethnic and socioeconomic disparities in HIV incidence. In these same communities, many patients at risk for HIV seek care for sexually transmitted infections (STIs) in Emergency Departments (EDs), but the structure of traditional ED care is poorly suited to address HIV prevention or provide PrEP. To advance the Prevent objective of the Ending the HIV Epidemic (EHE) initiative, ED2PrEP will leverage an implementation science approach to rigorously test two innovative strategies for increasing PrEP uptake among patients seeking STI care in EDs in one of the 48 EHE-identified geographic hotspots.