Aim Removal of eschar (debridement) is an essential and early step in the treatment of deep burns. Enzymatic debridement by NexoBrid® is a relatively new non-surgical tool for early, individualized and selective debridement which adds some advantages compared to surgical standard techniques known as standard of care (SOC). Nevertheless, until now it is not represented and calculated in the pricing system for German hospitals (G-DRG system), and an own operative procedure key (OPS) is lacking. The objective of this empiric cost study was to compare treatment cost of enzymatic debridement by NexoBrid® and SOC based procedures and to analyse the impact of improved burn wound care using NexoBrid® on total treatment costs of burn patients. Method The analysis is based on two different cost simulation models, the Average Outcome Model and the Defined Patient Model. Based on the results of a randomized phase III trial and treatment costs specified in the pricing system for German hospitals (G-DRG system), total costs of NexoBrid® based treatments were compared to those of SOC to determine cost saving potentials (Average outcome model). In addition, distinct burn wound treatment pathways common in clinical practice were assigned to actual treatment costs to allow economic considerations (Defined Patient Model). Results Using NexoBrid® cost savings are inversely related to the treated total burned surface area (1–15% TBSA) and directly related to the savings in burn centre stay (up to 6.5 days) (Average Outcome Model). Based on quantitative and qualitative aspects, three quarter of all cases in the range of 5% to 15% TBSA burned are in favour of NexoBrid®. Main cost drivers are LOS and ICU stay (45–80% of total costs). NexoBrid® becomes a more powerful cost driver with increasing TBSA treated. If NexoBrid® completely substitutes for SOC, the total cost per patient can be reduced by nearly 30% (treatment of 5% TBSA) or are in the range of SOC costs (treatment of 15% TBSA) (Defined Patient Model). Highest costs are generated when enzymatic and surgical methods for debridement are combined and an increased LOS or ICU stay is indicated. Conclusion Cost advantages of enzymatic debridement by NexoBrid® may emerge in cases with low or medium burned and treated surface area when costs for enzymatic debridement remain below the costs for SOC (excision plus autografting). Even in more severe cases (15% TBSA burned) total costs of basic NexoBrid®-based treatment pathways do not exceed costs of comparable SOC pathways. In addition, enzymatic debridement by NexoBrid® can be successfully applied as a strategic tool in order to reduce surgical procedure time and OR room capacity and making use of the redundant capacity for further surgical cases reimbursement. Beside these quantitative aspects that may improve overall economic efficiency, qualitative improvements of burn wound care must be considered separately from this analysis.