The removal of necrotic tissue with enzymatic debriding agents such as papain–urea copper chlorophyllin (PUC) can accelerate wound healing, but it is not known if the use of such agents has any effect on the quality of healing. The purpose of this study was to compare re-epithelialization and overall wound healing in acute, infected wounds treated with either PUC or moist wound care. Twenty full-thickness wounds were created on the dorsum of pigs. Following hemostasis, the wounds were contaminated with wound-isolated bacteria and then dressed with either a moist dressing alone or PUC and a moisture-retentive dressing. Wounds were evaluated for epithelialization and biopsies were obtained for microscopic evaluation on days 1, 4, 8, 11, 14, 18, and 21 postsurgery. Re-epithelialization in wounds treated with PUC was similar to those treated with moist wound care, suggesting no impairment of healthy tissue formation with PUC. Microscopic examination revealed more keratinocytes and a greater depth of rete pegs in the epidermis of PUC-treated wounds. These wounds also had more extensive blood vessel formation (verified with CD31 and von Willebrand Factor staining) at all examined time points. Higher VEGF levels were also seen in the wound fluid from PUC-treated wounds as compared to wounds treated with moist dressings. In conclusion, the healing in PUC-treated wounds appeared to be more complete based on the number of keratinocytes present in the epidermis, the more extensive rete peg formation, and greater degree of vascularization.