To evaluate the effect of negative pressure wound therapy (NPWT) on deep infection rate in open tibial fractures. DESIGN: Retrospective cohort study. Data was collected from medical records and radiographs. SETTING: Two level-1 trauma centers. PATIENTS/PARTICIPANTS: Patients who sustained an open tibial fracture which underwent delayed soft tissue coverage between January 2002 and December 2007 were included. Exclusion criteria included open fractures receiving a combination of NPWT and conventional dressings, fractures which were treated with a primary amputation, and fractures associated with mortality. INTERVENTION: NPWT with reticulated open cell foam or conventional dressings at surgeon s discretion. MAIN OUTCOME MEASUREMENT: Deep infection rate. RESULTS: A total of 229 open tibial fractures in 220 patients met the inclusion criteria and received either NPWT (166/229-72 ) or conventional dressings (63/229-28 ). There was a decreased rate of deep infection in the NPWT group compared with the conventional dressing group [8.4 (14/166) vs. 20.6 (13/63); P = 0.01]. Univariate predictors of deep infection included Gustilo type odds ratio (OR): 3.13 [95 confidence interval (CI): 1.74-5.64]; P <0.001 and use of NPWT [OR: 0.35 (95 CI: 0.16-0.80); P = 0.01]. When adjustment was performed for Gustilo type with multivariate analysis, use of NPWT was found to reduce the risk of deep infection by almost 80 [OR: 0.22 (95 CI: 0.09-0.55); P = 0.001]. CONCLUSIONS: These results suggest that NPWT reduces the rate of deep infection when used for the dressing of traumatic wounds in open tibial fractures.