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Chronic, nonhealing wounds consume a great deal of healthcare resources and are a major public health problem, associated with high morbidity and significant economic costs. Skin grafts are commonly used to facilitate wound closure. The grafts can come from the patient's own skin (autograft), a human donor (allograft), or from a different species (xenograft). A fish skin xenograft from cold‐water fish (Atlantic cod, Gadus morhua) is a relatively recent option that shows promising preclinical and clinical results in wound healing. Chronic wounds vary greatly in etiology and nature, requiring large cohorts for effective comparison between therapeutic alternatives. In this study, we attempted to imitate the status of a freshly debrided chronic wound by creating acute full‐thickness wounds, 4 mm in diameter, on healthy volunteers to compare two materials frequently used to treat chronic wounds: fish skin and dHACM. The purpose is to give an indication of the efficacy of the two therapeutic alternatives in the treatment of chronic wounds in a simple, standardized, randomized, controlled, double‐blind study. All volunteers were given two identical punch biopsy wounds, one of which was treated with a fish skin graft and the other with dehydrated human amnion/chorion membrane allograft (dHACM). In the study, 170 wounds were treated (85 wounds per group). The primary endpoint was defined as time to heal (full epithelialization) by blinded assessment at days 14, 18, 21, 25, and 28. The superiority hypothesis was that the fish skin grafts would heal the wounds faster than the dHACM. To evaluate the superiority hypothesis, a mixed Cox proportional hazard model was used. Wounds treated with fish skin healed significantly faster (hazard ratio 2.37; 95% confidence interval: (1.75–3.22; p = 0.0014) compared with wounds treated with dHACM. The results show that acute biopsy wounds treated with fish skin grafts heal faster than wounds treated with dHACM. [ABSTRACT FROM AUTHOR]