ABSTRACT We will adapt and pilot test a technology-enabled, primary care-based, health literacy strategy to empower women with increased vulnerability to HIV to make informed decisions about PrEP. Nearly 20% of new HIV infections in the United States (US) occur among cisgender women, with women of color disproportionately affected. Pre-exposure prophylaxis (PrEP) is a safe, effective, and empowering option for HIV prevention women can initiate and use without partner negotiation. Yet most women are unaware PrEP is an option for them. With primary care representing the frontline of healthcare for most adult women, it is an ideal setting to promote PrEP awareness and informed decision-making. Importantly, women themselves have asked for PrEP discussions to be normalized in primary care and multiple studies have shown that women value talking with clinicians about PrEP. Unfortunately, many primary care providers (PCPs) lack the time, resources, and experience needed to counsel women on PrEP during busy, routine visits. Our proposed R34 Encouraging Multiple PrEP Options for Women Engaged in PRimary Care (EMPOWER) therefore offers a pragmatic and innovative approach to the delivery of PrEP information to women in primary care. The EMPOWER strategy addresses well-documented barriers and `missed opportunities' for HIV prevention among cisgender women and supports informed PrEP decision-making by: 1) identifying women who may benefit most from PrEP via an electronic health record (EHR)-based algorithm that utilizes available EHR data on HIV risk factors (i.e. bacterial sexually transmitted infection, Hepatitis C diagnosis, substance use, intimate partner violence); 2) delivering understandable, actionable, and non-stigmatizing PrEP education, in multiple formats and languages, directly and securely to women via the patient portal; 3) enabling women to discreetly self-schedule a visit to discuss PrEP options with either their own PCP or with a female PCP who has years of experience in PrEP delivery; and 4) supporting PCP counseling via clinical decision support that provides standardized, patient-centered language to guide PrEP discussions and `smart sets' to facilitate PrEP prescribing, when desired. Our specific aims are to: 1) Adapt and coordinate the EMPOWER strategy to support informed decision-making among diverse cisgender women with increased vulnerability to HIV seen in primary care; 2) Pilot test the efficacy of the EMPOWER strategy, compared to an attention control, on PrEP knowledge, stigma, and future intention to use PrEP; and 3) Assess the reach, adoption, implementation, and maintenance of EMPOWER components. EMPOWER will be evaluated in Cook County, an `Ending the HIV Epidemic' priority area. The study will be meaningfully informed by a community advisory board of diverse women, a scientific advisory board of clinicians and experts, and a community collaboration board of local organization leaders in the field of HIV.