We describe, to our knowledge, the first case of limb-threatening necrotizing alternariosis whose limbs were successfully salvaged by adjunctive hyperbaric oxygen therapy (HBO2). This 58-y-old patient was immunocompromised with both diabetes and Cushing's syndrome. She suffered from necrotizing soft tissue infection of both legs caused by Alternaria. It was impossible to halt the progression of the invasive infection with standard anti-fungal treatment and aggressive surgical debridement. After the use of HBO2, the wound was stabilized and eventually healed. Adjunctive HBO2 in this case has demonstrated its role in the treatment of complicating necrotizing soft tissue infection caused by invasive fungal infection. The possible mechanisms may be the potentiation of immune responses and the enhancement of fibroblast proliferation.