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OBJECTIVE:: To present the first long-term results of Szilagyi III vascular infections treated by negative pressure wound therapy (NPWT) with graft preservation. BACKGROUND DATA:: Szilagyi III infections are usually treated by graft/artery excision and secondary vascular/plastic reconstruction. Small series treated with NPWT without graft removal are reported with good short-term to midterm results. METHODS:: The outcomes of 44 polymorbid patients (mean age = 62 years) with Szilagyi III infections from 2002 to 2009 were analyzed. Thirteen of forty-four required intensive care unit treatment. Forty grafts (prosthetic = 24, vein = 3, biological = 13) and 9 native arteries were involved. Negative pressure wound therapy (VAC; KCI International, Amstelveen, Netherlands) was applied directly on grafts/arteries (negative pressure = 50-125 mm Hg) after radical debridement of infected tissue. Antibiotic treatment was initiated and adapted according to microbiology. RESULTS:: Median duration of NPWT was 33 days (IQR: 20-78), of hospital stay 32 (IQR: 20-82) days. All patients survived 30 days. One-year mortality was 16% (7/44). Long-term mortality after a mean follow-up of 43 months (SD: 21) was 41% (18/44).Complete wound healing was achieved in 91% (40/44). In 37 of 44 patients, grafts were preserved long-term without reinfection. There was no statistically significant difference in outcome between the various graft types involved. CONCLUSIONS:: Vascular graft/arterial preserving treatment with NPWT in Szilagyi III infections was safe and effective with a very low short-term mortality. The majority of infected grafts were preserved without reinfection during a mean long-term follow-up of 4 years. This new treatment algorithm avoids major reconstructive surgery and should be used when dealing with Szilagyi III vascular infections