Background/Objective: Evidence for the relevance, effectiveness, and socio-cultural benefits of eHealth interventions with First Nations peoples is growing. In Australia, a research program is preparing a best practice framework (BPF) for eHealth with Aboriginal and Torres Strait Islander people [1]. The 7 phases aim to establish the themes and characteristics of culturally safe eHealth, as voiced by Aboriginal and Torres Strait Islander people. Methods: A systematic literature review and scoping review were conducted (Phases 1 and (ii) what guidelines or best practice evidence should inform eHealth interventions with Aboriginal and Torres Strait Islander people. PROSPERO and Open Science Framework protocols were registered. Search strategies incorporated variations of ‘eHealth’; ‘Aboriginal and Torres Strait Islander health’; ‘guidelines, ethics’. Database searches included WebofScience, Scopus, Cochrane, Embase, CINAHL, PubMed, PsycINFO, plus grey literature. Screening, data extraction and quality assessments were conducted by 3 authors, with narrative analysis to generate themes (Phase 3). Modified Delphi processes will confirm final themes and principles of the BPF (Phases 4-6). Delphi participants will include stakeholders of eHealth feasibility trials, subject matter experts, and community-controlled partners with expertise in Aboriginal and Torres Strait Islander health. Results: The BPF scientific protocol was published in June 2022 [1]. Phases 1&2 commenced November 2022 with findings on-track for release in early 2023. In December 2022, qualitative data collection was completed for several eHealth feasibility trials with Aboriginal and Torres Strait Islander communities. Key findings from stakeholders will contribute to subsequent Delphi processes scheduled for May 2023. Dissemination of the foundational BPF is expected December 2023 (Phase 7). This presentation will highlight key findings from completed research phases. Conclusions: A BPF will contribute to rigorous eHealth innovations that promote genuine co-design, ensure cultural safety and clinical effectiveness for Aboriginal and Torres Strait Islander people. [1]doi:10.2196/34904