BACKGROUND:Split thickness skin grafting (SSG) is an important modality for wound coverage; however, it leads to donor site morbidity. Epidermal grafting (EG) is a promising option for autologous skin grafting which offers minimal donor site morbidity, though it is not known if EG is an effective clinical alternative for SSG. This study compared the efficacy of EG as an alternative to SSG in terms of wound healing outcomes, donor site morbidity, patient satisfaction and adverse events. METHODS:EPIGRAAFT is a Phase 2, randomized, open-label trial with two parallel groups: EG and SSG. Patients referred for skin grafting with a healthy granulating wound bed were included. The co-primary endpoints were the proportion of wounds healed and donor site healing time. The secondary endpoints include donor site morbidity measured using Vancouver Scar Scale, mean time for complete wound healing, patient satisfaction assessed using a validated skin grafting questionnaire and incidence of adverse events. RESULTS:Of the 61 patients screened, 44 patients were randomized. There was no difference in the proportion of wounds healed at 6 weeks (p=0.366) and 3 months(p=0.24) as well as the mean time for wound healing (p=0.12). EG resulted in lower donor site morbidity (p=0.001), faster donor site healing time (EG: 4.86 days vs. SSG: 21.32 days) (p<0.0001), and higher overall satisfaction (p<0.001). There were no adverse events reported. CONCLUSION:This study demonstrated that EG has superior donor site outcomes with faster donor site healing and lower morbidity compared to SSG, while having comparable wound healing outcomes. Patients receiving EG also experienced higher donor site satisfaction compared to SSG. ClinicalTrials.gov identifier: NCT02535481.