The aim of our study was to analyze the aesthetic and functional outcome in the radial forearm free flap donor site using a simple split thickness skin grafting (STSG) closure compared with the use of dermal scaffold supporting the STSG closure. The study analyzed 18 patients, divided in 2 groups based on the donor site closure modality. In STSG group, a simple STSG was used to cover the defect. In the DS + STSG group, the defect was covered by the use of dermal substitute (MatriDerm) supporting the STSG. Groups were compared on the following outcome variable: scar status; hand function; circumferences at most proximal and most distal point of the graft. All patients were followed up 1, 6, and 12 months post-operative. Nine patients from STSG group showed a difference in circumference between the operated and contralateral limbs respectively of 2.9 mm proximal and 1.2 mm distal; in the 9 patients of DS + STGS group the difference was respectively of 1.2 mm proximal and 1.3 mm distal. Welch unequal variances t-test demonstrated statistical significance of the values with P < 0.004 (P < 0.5). The average VSS was 1.82 ± 0.2 for STSG group and 1.75 ± 0.2 for DS + STGS group. The DASH score was 21.8% in STSG group and 19.4% in DS + STGS group. Our study shows that patients treated with Matriderm + STSG obtained a better result both in esthetic and functional outcomes.