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Over the last decade, the application of and indications for negative pressure wound therapy with reticulated open cell foam (NPWT/ROCF) as delivered by V.A.C.® Therapy (KCI, San Antonio, TX) have grown tremendously. This is particularly true in orthopaedic trauma in the management of injuries to the leg, ankle, and foot. This article reviews the evidence-based medicine in terms of NPWT/ROCF, as a method of reducing bacterial counts in wounds, as a bridge until definitive bony coverage, for treating infections, and as an adjunct to wound bed preparation and for bolstering split-thickness skin grafts, dermal replacement grafts, and over muscle flaps. NPWT/ROCF has been shown to be an adjunct to the mainstays of wound management. No significant complications have been noted in the categories of NPWT/ROCF discussed in this review. In addition, evidence supports a decrease in complex soft tissue procedures in grade IIIB open fractures when NPWT/ROCF is employed. Although more research needs to be done, NPWT/ROCF appears to provide clinical benefit for the treatment of these complex lower extremity wounds.