Previous commercially available negative pressure wound therapy (NPWT) systems with instillation (NPWTi) have typically delivered solutions continuously (without soak time) to the wound bed. However, recent studies have demonstrated the successful use of NPWTi using volumetric automated instillation during wound healing. We evaluated the efficacy of treating patients with upper and lower extremity and trunk wounds with automated NPWTi with a soak time using a less hydrophobic reticulated open-cell foam dressing (ROCF-V). Our therapy goal was to cleanse and prepare the wound for closure. Patient records from 01-Jan-2010 through 31-May-2013 were retrospectively reviewed. All patients received systemic antibiotics and wound debridement. Patient wounds were treated with NPWTi/ROCF-V with volumetric automated instillation of a cleansing solution (saline or polyhexanide) with a set soak time (range: 1-60 seconds) followed by NPWT (range: 1-2 hours). Forty-eight patients received NPWTi and were compared to a historical control group of 34 patients who received standard NPWT. Wilcoxon rank sum test (two-sided) was used for all comparisons. Our results showed significant differences (p<0.001) between the NPWTi and NPWT patients, respectively, for the following endpoints: mean surgical debridements in the operating room (2.0 vs 4.4 debridements), mean hospital stay (8.1 vs 27.4 days), and mean time to wound closure (4.0 vs 20.9 days). Patients treated with NPWTi also had a lower mean number of dressing changes (2.0 for NPWTi vs 4.7 for NPWT, p<0.0001) and treatment days (4.1 days of NPWTi vs 20.9 days of NPWT, p<0.0001). Most NPWTi patient wounds were closed by primary intention, flaps/grafts, or dermal substitutes. In this study, automated NPWTi appeared to assist in wound cleansing and exudate removal, which may have allowed for earlier wound closure compared to standard NPWT.