Inpatient (rather than outpatient) therapy may be better for patients with wounds that (1) are >10 cm² (2) have been present >52 weeks, (3) have not decreased in size by at least 1mm/edge/week), and (4) have documented counts of >105 bacteria. We postulated that improved outcomes could be achieved from surgical debridement and use of negative pressure wound therapy with instillation (NPWTi). During a 4-week period, 8 outpatients with wounds meeting the above 4 criteria were identified as non-progressors by a senior nurse. These patients were transitioned to an inpatient setting and underwent operating room debridement and NPWTi initiation. Quantitative bacterial cultures were taken after debridement and after one week of NPWTi with repeated cycles of 0.125% Dakin’s instillation with a 10 minute soak time followed by 1 hour of NPWT (-125mmHg). Wounds had been present for an average of 17.7 months; post-debridement average wound size was 84.25cm2. Based on post-debridement cultures, there were 3 (±1) types of bacteria in each wound, and of those bacteria, there were 3.7x106 (±4x106) colony forming units (CFUs). At one week, the average wound size was 81.2cm2 (p=0.07), and there were 2 (±1) types of bacteria (p=0.17) and 2.6x105 (±3x105) CFUs (p=0.07). All but one patient had successful skin graft. At one month, all wounds were at least 85% closed. We believe that debridement and NPWTi provided rapid wound bed preparation with near significant reduction in bioburden. Improved results may be achieved by increasing soak times or frequencies and utilizing a better topical wound solution. In this study, patients with wounds >80cm2 in size, ≥ 3 types of bacteria on quantitative culture, >105 bacteria, and duration greater than 1 year were well served by this algorithm.