Significant disparities in pre-exposure prophylaxis (PrEP) for HIV prevention exist in the U.S. with cisgender women making up a disproportionately low percentage of PrEP users compared to men. 60% of new HIV diagnoses among women are among Black women, the majority of whom reside in the South. Challenges exist at each step of the PrEP care continuum, including difficulty identifying cisgender women at highest risk for HIV who are most likely to benefit from PrEP, low self-perception of HIV risk, low levels of PrEP knowledge, and barriers to PrEP initiation and persistence. While there has been growing knowledge of interventions to increase PrEP use among men who have sex with men and transgender women, much less is known about successful strategies to increase uptake and support PrEP persistence among Black cisgender women. Through preliminary work, our team has identified a set of successful strategies for PrEP Optimization among Women to Enhance Retention and Uptake (POWER Up) in community health center (CHC) settings, consisting of routine PrEP education for Black cisgender women, standardized provider training, electronic medical record tools for identifying women who would benefit from PrEP and tracking PrEP outcomes, and PrEP navigation. With These POWER Up strategies, a CHC network in the Midwest has more than doubled PrEP uptake among Black cisgender women and maintained PrEP persistence rates above the national average. These strategies have not been studied in CHCs with a large population of Black cisgender women outside of the Midwest. Therefore, we propose to refine, implement, and evaluate the impact of a CHC-focused intervention to improve PrEP care continuum outcomes for Black cisgender women in the Southern US, using implementation science research methods. Guided by the Exploration, Preparation, Implementation and Sustainment (EPIS) implementation science framework, we will undertake the following aims: 1) Preparation: Adapt previously identified successful implementation strategies for engaging Black cisgender women in the PrEP care continuum in a Midwestern CHC for use in Southern CHCs. 2) Implementation: Via a hybrid type II design using the RE-AIM framework, measure the implementation and effectiveness outcomes of the adapted interventions in the Southern United States compared to the approach in the Midwest. We will complete a stepped wedge randomized controlled trial in 16 CHCs in the Midwest and South. 3) Sustainment and Spread: Develop an implementation guide that can be utilized across Southern U.S. jurisdictions to improve PrEP care continuum engagement among Black cisgender women reflecting the knowledge gained through adaptation. This will allow for rapid dissemination and replication of these strategies to improve PrEP care continuum outcomes among Black cisgender women.