In the United States, over 30,000 patients are hospitalized annually because of burn injuries. 1 These injuries are often slow to heal, leading to lengthy hospitalization time, increased health care costs, and lower quality of life. Burnassociated impaired healing is linked to deregulated inflammation at the site of the injury driven by skin-resident and infiltrating peripheral immune cells. [2][3][4] Although certain inflammatory responses impair healing, 5-8 others promote tissue repair and reconstruction. [7][8][9][10][11][12] Thus, defining prorepair pathways associated with inflammation is a crucial step for the development of successful therapeutic strategies.Leukotrienes are short-lived lipid mediators derived from the conversion of arachidonic acid by 5-lipoxygenase and consist of leukotriene B 4 and the cysteinyl leukotrienes: leukotriene C 4 , leukotriene D 4 , and leukotriene E 4 . 13,14 [See Figure, Supplemental Digital Content 1, which shows the 5-lipoxygenase (5-LO) pathway. A variety of stimuli can induce the release of arachidonic acid from membrane phospholipids by cytosolic phospholipase A2 (cPLA2; gene name, Pla2g4a). 5-Lipoxygenase (gene name, Alox5), together with 5-lipoxygenase activating protein (FLAP; gene name, Alox5ap), converts free arachidonic acid to form the unstable intermediate leukotriene A4 (LTA4). Leukotriene A4 can be either hydrolyzed by leukotriene A4 hydrolase (LTA4H; gene name, Lta4h) to form leukotriene B4 (LTB4) or conjugated to reduced glutathione by leukotriene Background: Burns are severe injuries often associated with impaired wound healing. Impaired healing is caused by multiple factors, including dysregulated inflammatory responses at the wound site. Interestingly, montelukast, an antagonist for cysteinyl leukotrienes and U.S. Food and Drug Administration approved for treatment of asthma and allergy, was previously shown to enhance healing in excision wounds and to modulate local inflammation. Methods: In this study, the authors examined the effect of montelukast on wound healing in a mouse model of scald burn injury. Burn wound tissues isolated from montelukast-and vehicle-treated mice at various times after burn injury were analyzed for wound areas (n = 34 to 36), reepithelialization (n = 14), inflammation (n = 8 to 9), and immune cell infiltration (n = 3 to 6) and proliferation (n = 7 to 8). Results: In contrast to previously described beneficial effects in excision wounds, this study shows that montelukast delays burn wound healing by impairing the proliferation of keratinocytes and endothelial cells. This occurs largely independently of inflammatory responses at the wound site, suggesting that montelukast impairs specifically the proliferative phase of wound healing in burns. Wound healing rates in mice in which leukotrienes are not produced were not affected by montelukast. Conclusion: Montelukast delays wound healing mainly by reducing the proliferation of local cells after burn injury. (Plast. Reconstr. Surg. 150: 92e, 2022.) Clinical Relevance Statement: Al...