Introduction. Unresolved wound healing represents a major health care cost with a negative impact on patient quality of life, especially among oncology patients who exhibit a delay in the wound healing cascade due to chemotherapy and radiation. In order to address this problem, the author utilized negative pressure wound therapy (NPWT) with instillation and dwell time (NPWTi-d) to cleanse wounds of debris and help promote healing. Objective. The author examines the impact of NPWTi-d on multiple indicators of wound healing progress in 6 cancer patients with complex wounds and multiple comorbidities. Materials and Methods. The NPWTi-d was initiated with instillation of normal saline or 0.125% hypochlorite solution, which was allowed to dwell for 3 to 20 minutes, followed by 2 to 3.5 hours of -125 mm Hg continuous negative pressure. Dressing changes were performed every 2 to 3 days. Debridements, incision and drainage, and antibiotics were administered as necessary. Results. A total of 1 woman and 5 men (average age, 62 years; range, 53–78 years) presented with the following wounds: surgical dehiscence (n = 3), pressure injury (n = 1), chronic seroma (n = 1), and abdominal wall abscess (n = 1). Malignancy was not detectable in any wounds. Patient comorbidities included diabetes, hypertension, and past treatment for cancers. The NPWTi-d was applied for 1 to 2 weeks, after which the wounds exhibited a reduction in slough, an improvement in granulation tissue, and a decrease in wound volume. Wounds were closed with a flap or transitioned to conventional NPWT prior to discharge home or to a rehabilitation facility for outpatient recovery. Conclusions. As shown in this case series, NPWTi-d was a beneficial tool for cleansing the wound bed, thus creating a moist, closed wound environment conducive to healing. Using NPWTi-d supported the formation of a healthy wound bed and contributed to rapid, positive outcomes in this patient population.