Background: For years, surgical debridement with autografting has been considered the standard of care in the treatment of severe burns of the hand. However, in recent years, enzymatic debridement has increasingly been reported as a good alternative, especially for burns of the hand, as it selectively preserves viable tissue. In this study, we aim to evaluate the long-term function of the hand after enzymatic debridement in deep dermal burns. Methods: A retrospective chart review was conducted as well as measurements of subjective and objective outcome measures through physical examination and Disabilities of the Arm, Shoulder, and Hand (DASH), Patient and Observer Scar Assessment Scale (POSAS), and Vancouver Scar Scale (VSS) scores. Results: A total of 32 enzymatically debrided hands of 24 patients were included with a mean age of 42.4 ± 16.8 years and a mean follow-up of 31 months. Postoperatively, 19 of these could be managed conservatively using skin substitutes such as “Suprathel”, 13 had to undergo subsequent autografting. The mean DASH score for the entire study population was eight with a mean value of four in the conservatively managed group and fourteen in the autografted group. The mean Patient, Observer POSAS, and VSS values were nineteen, thirteen, and two. A total of 30 cases showed an effortless complete fist closure, and, also in 30 cases, patients attested to be satisfied with the esthetic appearance of the hand on being asked. Conclusions: The descriptive analysis of these results in our study population suggests that the enzymatic debridement of deep burns of the hand, especially combined with subsequent conservative management with skin substitutes, was associated with low long-term hand disability scores at a follow-up of two years.