Abstract Introduction Definitive closure with autograft, as a current standard of care, is a critical outcome in severe burn treatment. Harvest of donor skin for autograft is associated with pain, scarring and potential infection. New treatment modalities aim to reduce the amount of donor skin required to achieve definitive closure of the burn wound. A threshold that defines the clinically significant reduction in amount of harvested skin for the treatment of deep partial (DPT) and full-thickness (FT) burns is not available. This study convened a Delphi Consensus Panel (DCP) to determine this threshold. The DCP is an accepted method to synthesize opinions and feedback from experts and to systematically achieve consensus. Methods Panel members were burn physicians with ≥3 years of experience post-residency, with either a total career experience of caring for ≥1,000 patients or working in a facility with an annual volume of ≥200 patients and caring for ≥500 patients. Round 1 consisted of open-ended questions regarding clinical decision-making, use of skin substitutes (SS) in DPT and FT burn treatment, and what would constitute a clinically significant reduction in donor skin. Results Panelists reported using SS to promote healing and achieve definitive closure without autograft for DPT burns, and as a temporizing measure between excision and surgery for FT burns. Total body surface area (TBSA) affected by burn and burn location influenced SS use. For DPT and FT burns, other patient outcomes influencing treatment decisions were cosmesis, pain control, and reducing functional limitations. Almost all panelists reported that reduction in the amount of donor skin were important. As expected in Round 1, a range for the minimum percentage of donor skin reduction regarded as clinically significant was provided for DPT (20%-50%) and FT (10%-20%) burns. The main factors influencing these estimates were TBSA burned, patient outcomes, patient preference, and patient type. Final results will provide consensus estimates for clinical significance for donor skin reduction based on subsequent rounds. Conclusions Preliminary results indicate that reduction of the amount of donor skin is important to physicians with burn care experience, and the thresholds for clinical significant reduction in donor skin are influenced by patient outcomes and preferences, TBSA burned, and patient type. Applicability of Research to Practice These data will provide a research-based definition surrounding the clinical significance of new treatment modalities for severely burned patients.