: Burned tissue has traditionally been removed surgically, but the effectiveness of enzymatic debridement with NexoBrid has been reported in burn patients and has gained attention in recent years. This agent was approved for use in Japan in 2023. However, even in Japan, there have been few studies examining its effectiveness in patients with extensive burns. The purpose of this study was to analyze the association of combined NexoBrid and surgical excision with clinical outcomes in extensive burn patients. : Between January 2020 and December 2024, seventeen flame burn patients requiring surgical excision were divided into two groups based on whether NexoBrid was used. Clinical outcomes between the two groups were compared using the propensity score overlap weighting method to adjust for baseline differences. : Seven of the patients received combined NexoBrid and surgical excision. After weighting, NexoBrid was significantly associated with a shorter time to complete debridement of burned tissue (difference -4 days, 95% CI -5 to -2) and lower percentage of bacteremia (odds ratio 0.06, 95% CI 0.00 to 0.96). However, no significant differences were observed in the length of ICU stay, the amount of blood transfusion required for complete tissue removal, hospitalization costs, and in-hospital mortality. : Combining conventional surgical excision with enzymatic debridement may reduce the time required to complete debridement of burned tissue and decrease the rate of bacteremia. Further studies are needed to evaluate the effectiveness of NexoBrid combined with surgical excision in patients with extensive burns.