Reepithelialization of deep burns requires spontaneous or active removal or debridement of the necrotic eschar, as recently defined by the American Burn Association. Debrase is a bromelain-derived enzymatic preparation that has been shown to result in rapid and selective debridement of human and animal burns. The authors hypothesized that rapid debridement of deep dermal burns with Debrase would result in earlier reepithelialization of the remaining dermis in a porcine model. Eighty deep dermal contact burns measuring 10 by 20 mm were created on the back and flanks of anesthetized domestic pigs (25 kg) using a brass template preheated in boiling water (100 degrees C) that was applied to the skin for a period of 30 seconds. The template was applied using a spring-loaded device designed to control the amount of pressure applied to the skin by the template. Burns were randomized to a 4-hour topical application of Debrase (lyophilized dry enzyme dissolved and activated in a hydrating vehicle) (n = 40) or its hydrating vehicle (n = 40) followed by daily application of a petrolatum-based antibiotic ointment. Wounds were visually assessed and photographed daily. Four-millimeter full-thickness punch biopsies were obtained for histological analysis using hematoxylin and eosin staining by a board-certified dermatopathologist masked to burn therapy at 7, 11, 13, and 15 days after injury. The primary outcome was the percentage of the burns that were completely reepithelialized at each time point. Secondary outcomes were time to complete reepithelialization and the mean percentage of reepithelialization on microscopic analysis. A sample of 40 burns in each group had 80% power to detect a 20% difference in the percentage of completely reepithelialized burns (two tailed, P < .05). The percentage of completely reepithelialized burns was higher for Debrase than control burns at days 11 (40.9% vs 3.1%; P = .002), 13 (87.5% vs 50%; P = .007), and 15 (97.5% vs 77.5%, P = .018). The mean (SD) percentage reepithelialization of Debrase-treated burns at 7 days was higher than of control burns (47.6% [3.2] vs 0% [0]; P < .001). A larger number of cells in the epidermis and dermis of debrided burns stained positive for the proliferation antigen Ki-67. There was no evidence of any adverse events in the normal skin adjacent to the Debrase-treated burns. Rapid enzymatic debridement of deep partial-thickness burns with Debrase results in earlier reepithelialization and cellular proliferation in swine, when compared with carrier and topical antibiotic dressings alone.