The purpose of the study was to evaluate safety and feasibility of negative pressure wound therapy (NPWT) during aeromedical evacuation from a combat zone to a regional treatment center. A retrospective review of patients who received NPWT during aeromedical evacuation from Iraq or Afghanistan to Landstuhl Regional Medical Center (LRMC) was performed. Data were collected describing mechanism of injury; anatomic site of NPWT application; number of sites per patient; date and time of NPWT application; date, time, and wound condition on arrival and inspection at LRMC; and complications encountered during aeromedical evacuation. Broad definitions of complications were employed. Any reported malfunction of NPWT devices or need to reinforce NPWT dressings was abstracted. Presence of tissue under the dressing requiring debridement was defined as a minor complication. Major complications were defined as wound sepsis with systemic manifestations. A total of 218 patients who had received NPWT for 298 wounds (1.37 per patient) during aeromedical evacuation were identified. Most wounds were due to high-energy blast or ballistic mechanisms. Average time from NPWT application to removal was 53 hours (range, 18-133 +/- 22 hours). Complications occurred at 14% of NPWT sites and in 19% of patients receiving NPWT. Most recorded complications were minor (95%). Two patients who arrived at LRMC with fever and evidence of wound sepsis improved rapidly after additional operative debridement. In no case was failure of the NPWT device in flight specifically implicated in the genesis of a recorded complication. In-flight device problems were identified in seven cases. Four of these could not be repaired in flight and were clamped. Complications were not increased in this cohort. Use of NPWT during aeromedical evacuation appears safe and feasible in a large cohort of patients with high-energy injuries. Complications were consistent with severity of injury and not related to failure of NPWT.