Purpose Early case series reports of the use of a novel synthetic matrix – NovoSorb BTM – in the treatment of diabetes-related neuropathic and neuroischemic foot wounds have demonstrated promising clinical outcomes. A single-centre randomized control trial (RCT) was conducted to establish the efficacy of this novel therapy in a diabetes-related foot wound cohort. Methodology An RCT comparing the use of NovoSorb BTM plus usual standard of care (USOC) in the treatment of moderate to severe post-surgical diabetes-related foot wounds, compared with the USOC alone. Participant inclusion was limited to wounds of moderate to high severity as defined by SVS Wound, Ischemia and foot Infection (WIfI) grading system (grade 3 or 4). Primary outcomes were complete wound healing, and amputation rates at 12-month post treatment. Secondary outcomes included days to wound healing, wound surface area reduction, and infection. Results Between May 2022 and September 2024, a total of 64 participants were enrolled, with 32 progressing to BTM treatment plus USOC and 30 to USOC alone. Interim analysis of complete wound healing at 12-months was observed in 66.7 % of BTM-treated wounds compared with 56.5 % of USOC, however this was not statistically significant (P = 0.48). There were no significant differences observed in 12-month amputation rates between either group. Kaplan-Meier analysis of days to wound healing of wounds with a starting surface area (SA) of > 10cm2 observed a significant decrease in those wounds treated with BTM (191days) compared with USOC (319 days) (Log-Rank Sig. 0.04, 95 % CI 209, 300). Conclusion The significant reduction in days to complete wound healing in large SA wounds treated with NovoSorb BTM, compared with USOC, positions this novel technology as a useful new weapon in the limited armamentarium of treatment options for post-surgical diabetes-related neuropathic / neuroischemic wounds healing by secondary intention.