Dressings used to manage donor site wounds have up to 40% of patients experiencing complications that may cause suboptimal scarring. We evaluated the efficacy and safety of a portable electrospun nanofibrous matrix that provides contactless management of donor site wounds compared with standard dressing techniques. This study included adult patients who underwent an excised split-thickness skin graft with a donor site wound area of 10-200 cm 2. Patients were allocated into two groups; i.e., the nanofiber group managed with a nanofibrous polymer-based matrix, and the control group managed using the standard of care such as Jelonet® or Biatain® Ibu dressing. Primary outcomes were postoperative dermal healing efficacy assessed by Draize scores. The time to complete re-epithelialization was also recorded. Secondary outcomes included postoperative adverse events, pain, and infections during the first 21-days and extended 12-month follow-up. The itching and scarring were recorded during the extended follow-up (months 1,3,6,9,12) using Numerical-Analogue-Score and Vancouver scores, respectively. The nanofiber and control groups included 21 and 20 patients, respectively. The Draize dermal irritation scores were significantly lower in the nanofiber vs. control group (Z=-2.509; P=0.028) on the first postoperative day but became similar afterward (Z≥-1.62; P≥0.198). In addition, the average time to re-epithelialization was similar in the nanofiber (17.9±4.4 days) and control group (18.3±4.5 days) (Z=-0.299; P=0.764), so were postoperative adverse events, pain, and infection incidence, itching and scarring. The safety and efficacy of electrospun nanofibrous matrix are similar to standard wound care allowing its use as an alternative donor site dressing following the split-thickness skin graft excision.