Background: While the introduction of HIV pre-exposure prophylaxis (PrEP) as an HIV prevention strategy has allowed women to exercise more control over the reduction of HIV transmission rates, adolescent girls and young women (AGYW) in Sub-Saharan Africa continue to experience higher rates of HIV infections and bear the greatest disease burden. Understanding progress in PrEP uptake among AGYW would enhance risk reduction in this vulnerable population. The Determined, Resilient, AIDS-Free, Mentored and Safe women (DREAMS) Initiative plays a key role in this risk reduction strategy.Methods: We performed a retrospective qualitative study to explore facilitators and barriers to PrEP, specifically those effecting initiation and persistence, among AGYW enrolled in the DREAMS Initiative at Pamoja Community Based Organization (CBO) in Kisumu, Kenya. We conducted key informant interviews (n = 15) with Pamoja CBO staff, health care providers and community leaders. Additionally, we conducted focus group discussions with young women receiving PrEP (n = 40) and peer mentors (n = 12). We did thematic analysis using the Consolidated Framework for Implementation Research to identify emergent themes.Results: We found that the use of the safe space model, decentralization of PrEP support and delivery, peer mentors, proper linkage to local health care facilities, and the sensitization of parents and male sexual partners were among some of the facilitators to PrEP uptake. Barriers to initiation and persistence included stigma associated with the use of anti-retroviral dugs, distance to safe spaces, and limited testing and qualified health care workers for PrEP distribution and administration.Conclusions: Overall, community roll out of PrEP within the DREAMS Initiative was successful in part due to integration and layering of services (biological, behavioral and structural), increased self-efficacy among AGYW, enhanced inter-agency and multisectoral collaboration.