Pyoderma gangrenosum (PG) is a rare disease that presents as painful ulcerations with inflammation and undermining at the borders. The ulcers can occur anywhere on the body but are most commonly seen on the lower extremities. The etiology of PG is unknown, and there are no definitive diagnostic criteria; PG is a diagnosis of exclusion, which can present serious delays in treatment.Patients should be treated with an interdisciplinary approach with aggressive immunosuppression, treatment of any comorbidities, maximization of nutrition status, reconstructive surgery for treatment of the wound, and physical therapy for deconditioning.This article presents a case study of one patient treated with a porcine urinary bladder matrix and negative-pressure wound therapy; this treatment combination provided pain relief, coverage of the wound, an acceptable aesthetic outcome, and long-term stability.