Use of negative-pressure therapy (NPT) is a well-established therapy for chronic, open, contaminated wounds, promoting formation of granulation tissue and healing. The application of NPT after primary closure (ie, incisional NPT) has also been shown to reduce surgical site infection and surgical site occurrence in high-risk procedures across multiple disciplines. Incisional NPT is believed to decrease edema and shear stress, promote angiogenesis and lymphatic drainage, and increase vascular flow and scar formation. Incisional NPT may be considered when there is a high risk of surgical site occurrence or surgical site infection, particularly in procedures with nonautologous implants, such as hernia mesh or other permanent prosthetics. Here we discuss the proposed physiologic mechanism as demonstrated in animal models and review clinical outcomes across multiple specialties.