Chronic wounds in previously radiated tissue are challenging to treat. In this article, the authors describe 3 such wounds that failed to heal despite multiple treatments with traditional wound healing methods. Treatment with porcine urinary bladder matrix, an extracellular matrix material, was initiated to facilitate epithelialization and promote wound healing. MatriStem powder (ACell, Inc, Columbia, Maryland), MatriStem (ACell, Inc) sheet, and DuoDerm (ConvaTec, Skillman, New Jersey) were applied biweekly and resulted in complete wound closure within 3 weeks of initial application for all 3 cases. All wounds remained closed 9 months following treatment, suggesting a role for urinary bladder matrix in the management of chronic wounds in the setting of irradiated tissue.