There have been no studies evaluating incisional NPWT as a prophylactic treatment to prevent infection and wound dehiscence of high-risk surgical incisions. Our data demonstrate that there is a decreased incidence of wound dehiscence and total infections after high-risk fractures when patients have NPWT applied to their surgical incisions after closure. There is also a strong trend for decreases in acute infections after NPWT. Based on our data in this multicenter prospective randomized clinical trial, NPWT should be considered for high-risk wounds after severe skeletal trauma.