Angioinvasive fungal infections have a significant morbidity and mortality in the immunocompromised host. Massive burns produce a profound derangement in cellular immunity along with a loss of cutaneous barrier function. Treatment of fungal burn wound infections poses a difficult therapeutic challenge. We present a new method of treatment for angioinvasive fungal infections with nystatin powder at a concentration of 6,000,000 units/g. It proved to be efficacious in four consecutive severely burned patients affected by massive angioinvasive fungal infection. Both superficial and deep tissue infections were eradicated without any other therapeutic interventions or adverse effects on wound healing.