Introduction. Pyoderma gangrenosum (PG) is a rare, ulcerative dermatosis that is part of a systemic auto-inflammatory process. The overall incidence of PG is 5.8 per 100 000 individuals and it is associated with an increased mortality rate compared with the general population. Due to the pathergy phenomenon—present in 20% to 30% of cases—traumatic events, such as debridement or surgery, are often avoided in these patients. This report is on the use of negative pressure wound therapy with instillation and dwell time (NPWTi-d) combined with a reticulated open cell foam dressing with through holes (ROCF-CC) to achieve debridement and granulation in a lower extremity PG wound. Case Report. A known patient with history of neuropathic arthritis, systemic lupus erythematosus, and cryoglobulinemic vasculitis presented with worsening of his lower extremity wound including new onset pain, odor, and purulent discharge. Negative pressure wound therapy with instillation and dwell time using a hypochlorous acid solution and a ROCF-CC was initiated. Significant decrease in necrotic tissue was noted by day 4, with improved granulation tissue growth by day 25. No pathergy occurred in this case. Conclusions. The use of NPWTi-d with ROCF-CC demonstrated positive debridement effects on this PG wound.