Introduction. The management of chronic, nonhealing wounds in patients with multiple comorbidities continues to be a challenge for health care practitioners. Chronic wounds typically do not progress through the normal phases of wound healing and generally remain stagnant during the inflammatory phase, resulting in an increase in proteolytic enzymes with degradation of the extracellular matrix. Bacterial biofilm has been documented to be one of the main factors delaying wound healing, resulting in the prolongation of the inflammatory phase. Objective. In order to control biofilm formation, sequester proteolytic enzymes, and provide a biocompatible scaffold to support healing, the investigators utilize a purified collagen matrix containing polyhexamethylene biguanide (PCMP) in a case series of 9 wounds on 8 patients with multiple comorbidities who did not respond to previous conventional or adjuvant therapy. Materials and Methods. Wound etiologies included 3 pressure ulcers, 1 diabetic foot ulcer, 1 venous leg ulcer, 2 postsurgical wound dehiscences, 1 ulcer secondary to calciphylaxis, and 1 traumatic wound secondary to hematoma. The average wound size at the first PCMP application was 34.0 cm2, and the wounds were present for an average of 9.2 weeks prior to the first PCMP application. Results. Patients received an average of 5.8 PCMP applications. Of the 6 wounds that healed, average time to closure from the first PCMP application was 10 weeks. The remaining 3 wounds demonstrated improved wound appearance with 100% granulation tissue and an average area reduction during PCMP treatment of 61.4%. Conclusions. This case series demonstrated that PCMP along with good wound care supported both wound closure and improvements in wound bed condition and area reduction on recalcitrant, nonhealing wounds of various etiologies.