Upper limb burn treatment represents a major medical and surgical challenge. Enzymatic escharolysis is a rather new technique to treat thermal burns in an easy and rapid way, as an alternative to the standard of care. The aim of the study was to investigate and describe the efficacy of treatment of upper limb burns with NexoBrid® in a non-burn referral center. All patients suffering from upper limb burns and admitted within 36 hours to the Hand and Microsurgery Unit of the ASST Sette Laghi from December 2016 to June 2018 were enrolled in the study. A retrospective analysis was performed, evaluating time to wound healing, time of hospitalization, and scar aesthetic appearance with patient and observer scar assessment scale (POSAS) and disabilities of the arm, shoulder and hand score (DASH). A total of 18 patients with burns involving the upper limb from December 2016 to June 2018 were treated. The mean TBSA% involved was 3%; 4 out of 18 patients suffered circumferential burns. The mean POSAS score was 14; the mean DASH score at 6-month follow up was 21, while it reduced to 11 at the last follow up visit. Enzymatic escharolysis is a novel, rapid and selective treatment option that allows early physiotherapy with overall satisfying functional results. We believe that enzymatic escharolysis should be considered, in most cases, as the standard of care in the treatment of upper limb burn wounds in non-burn referral centers.