OBJECTIVES: To evaluate the utility of negative-pressure wound therapy (NPWT) in the setting of high-energy open tibial shaft fractures. DESIGN, SETTING, AND PATIENTS/PARTICIPANTS: This was a retrospective consecutive series in a level 1 university-based trauma center. Forty-nine consecutive patients presenting to a level 1 trauma center between 1996 and 2004 with 50 grade/type III open tibial shaft fractures were assessed. INTERVENTION: The open wounds associated with each fracture were each treated with NPWT before definitive wound closure or coverage. MAIN OUTCOME MEASUREMENTS: Infection rate, need for amputation after attempted definitive coverage, problems with bony healing requiring surgical intervention, reoperation rate after definitive coverage, and the type of definitive coverage required. RESULTS: The overall infection rate for all grade/type III open fractures was 15 of 50 fractures (30%), with 11 of 50 (22%) requiring repeated surgery for infection. The infection rate was 12.5% for grade/type IIIA open fractures, 45.8% for grade/type IIIB, and 50% for grade/type IIIC. Twenty-four of 50 fractures (48%) required subsequent surgery to facilitate fracture healing. Five fractures required amputation after attempted coverage. Seven of 24 fractures initially classified as grade/type IIIA and 10 of 24 fractures initially classified as grade/type IIIB ultimately required free tissue transfer or rotational muscle flap coverage. CONCLUSIONS: Infection and nonunion rates with the use of NPWT for temporary coverage of wounds associated with grade/type III open tibial shaft fractures are similar to those of historical controls, but this technique may be beneficial in decreasing the need for free tissue transfer or rotational muscle flap coverage.