Background <p>HIV pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool, yet uptake and retention among populations vulnerable to HIV acquisition remain below target levels. Telehealth has emerged as a promising strategy to overcome barriers to accessing PrEP. However, significant gaps remain in our understanding of the implementation of telehealth programs for PrEP. This study examines implementation barriers and facilitators in the Philadelphia TelePrEP Program (PTP), assesses program acceptability, usability and satisfaction, and investigates associations between client characteristics and implementation outcomes.</p> Methods <p>We conducted a mixed-methods evaluation from October 2023 to February 2025 of the PTP using web-based surveys with 113 participants and in-depth interviews with 5 staff members. We assessed implementation outcomes (i.e., program acceptability, usability, and satisfaction) and explored implementation determinants through qualitative analysis guided by the Consolidated Framework for Implementation Research. We used linear regression to examine associations between sociodemographic and clinical characteristics of participants and implementation outcomes.</p> Results <p>Survey participants were predominantly cisgender men with diverse racial/ethnic backgrounds. Participants reported high levels of acceptability, usability, and satisfaction with the PTP, though those with less than full-time employment reported significantly lower acceptability and usability compared to those with full-time employment. Mixed-methods analysis identified patient navigators as a central facilitator of program success, with both staff and clients emphasizing their role in creating a supportive, stigma-free care environment. Key implementation barriers included billing complexity, platform integration challenges, and privacy concerns. Although designed as a fully remote program, substantial demand for in-person services (particularly for injectable PrEP) emerged as a central implementation theme, underscoring the need for flexible hybrid service models. Staff also identified gaps in reaching priority populations, including Black and Latine communities, despite the program’s broad digital outreach efforts.</p> Conclusions <p>TelePrEP programs can achieve high user satisfaction when supported by dedicated navigation services and flexible care options. However, realizing the full potential of this model may require additional strategies to enhance program reach, streamline multi-organizational coordination, and support hybrid service models that accommodate diverse patient preferences and socioeconomic circumstances.</p>