Autonomous Artificial Intelligence (AI) has the potential to reduce disparities, improve quality of care, and reduce cost by improving access to specialty diagnoses at the point-of-care. Diabetes and related complications represent a significant source of health disparities. Vision loss is a complication of diabetes, and there is extensive evidence supporting annual eye exams for prevention. Prior to the use of autonomous AI, store-and-forward imaging approaches using remote reading centers (asynchronous telemedicine) attempted to increase diabetes related eye exams with limited success. In 2018, after rigorous clinical validation, the first fully autonomous AI system [LumineticsCore™ (formerly IDx-DR), Digital Diagnostics Inc., Coralville, IA, United States] received U.S. Food and Drug Administration (FDA)De Novoauthorization. The system diagnoses diabetic retinopathy (including macular edema) without specialist physician overread at the point-of-care. In addition to regulatory clearance, reimbursement, and quality measure updates, successful adoption requires local optimization of the clinical workflow. The general challenges of frontline care clinical workflow have been well documented in the literature. Because healthcare AI is so new, there remains a gap in the literature about challenges and opportunities to embed diagnostic AI into the clinical workflow. The goal of this review is to identify common workflow themes leading to successful adoption, measured as attainment number of exams per month using the autonomous AI system against targets set for each health center. We characterized the workflow in four different US health centers over a 12-month period. Health centers were geographically dispersed across the Midwest, Southwest, Northeast, and West Coast and varied distinctly in terms of size, staffing, resources, financing and demographics of patient populations. After 1 year, the aggregated number of diabetes-related exams per month increased from 89 after the first month of initial deployment to 174 across all sites. Across the diverse practice types, three primary determinants underscored sustainable adoption: (1) Inclusion of Executive and Clinical Champions; (2) Underlining Health Center Resources; and (3) Clinical workflows that contemplate patient identification (pre-visit), LumineticsCore Exam Capture and Provider Consult (patient visit), and Timely Referral Triage (post-visit). In addition to regulatory clearance, reimbursement and quality measures, our review shows that addressing the core determinants for workflow optimization is an essential part of large-scale adoption of innovation. These best practices can be generalizable to other autonomous AI systems in front-line care settings, thereby increasing patient access, improving quality of care, and addressing health disparities.