Collagen-based dressings are of great interest in wound care. However, evidence supporting their mechanism of action in a wound setting in vivo is scanty. This work providesfirst results from a pre-clinical swine model of excisional wounds elucidating the mechanism of action of a modified collagen gel (MCG) dressing. Following wounding, wound-edge tissue was collected at specific time intervals (3, 7, 14, and 21 days post-wounding). On day 7, histological analysis showed significant increase in the length of rete ridges suggesting improved biomechanical properties of the healing wound tissue. Rapid and transient mounting of inflammation is necessary for efficient healing. MCG significantly accelerated neutrophil and macrophages recruitment to the wound site on day 3 and day 7 with successful resolution of inflammation on day 21. MCG induced MCP-1 expression in neutrophil-like HL-60 cells in vitro. In vivo, MCG treated wound tissue displayed elevated VEGF expression. Consistently, MCG-treated wounds displayed significantly higher abundance of endothelial cells with increased blood flow to the wound area indicating improved vascularization. This observation was explained by the finding that MCG enhanced proliferation of wound-site endothelial cells. In MCG-treated wound tissue, Masson’s Trichrome and Picrosirius red staining showed higher abundance of collagen and increased collagen type I:III ratio. This work presents first evidence from a pre-clinical experimental setting explaining how a collagen-based dressing may improve wound closure by targeting multiple key mechanisms as compared to standard of care i.e., Tegadem treated wounds. The current findings warrant additional studies to determine whether the responses to the MCG are different from other modified or unmodified collagen based products used in clinical setting.