Extension for Community Healthcare Outcomes (Project ECHO) is a telementoring program for health professionals that uses adult learning techniques and interactive video technology to connect distal community providers with specialist and multidisciplinary teams in real-time collaborative sessions. We examine the adoption, implementation, and sustainability of ECHO programs at four academic medical centers through case studies based on structured interviews. The study and its analysis are informed by the Diffusion of Innovation theory and the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. We found that early adopters became aware of ECHO by chance and were persuaded through observations to adopt ECHO. Finding a home for ECHO was an important initial adoption decision. Five context factors influence the implementation of ECHO: Funding, networks, staffing processes, leadership, and individual characteristics of staff. Sustainability requires ongoing funding, which itself may rely on evidence of outcomes. Findings from this study can inform the implementation of Project ECHO at other academic medical centers and extend to decisions to adopt, implement, and sustain similar telementoring programs designed to close the research-practice care gap between communities and academic medical centers.