Compared to other states in the United States, Mississippi has the lowest uptake of PrEP relative to the number of people newly diagnosed with HIV in the state. Open Arms Healthcare Center is the largest provider of PrEP in Mississippi, and has systematically documented PrEP eligibility, offers, and acceptance (ie, agreed to undergo a clinical PrEP evaluation) from 2017 to mid-2020. In encounter-based analyses, we examined factors associated with PrEP acceptance. Among 721 encounters where patients were eligible for PrEP, staff offered PrEP at 680 (94%) of encounters (526 unique individuals); individuals accepted a PrEP offer at 58% of encounters. Accepting a PrEP offer was lowest (15.8%) among transgender/non-binary individuals and highest (93.3%) among individuals who reported having sex partners living with HIV. This clinic's model worked to offer PrEP to a highly impacted population, though there is a need to enhance PrEP acceptance for key groups such as transgender/non-binary individuals.