OBJECTIVE: To evaluate the relative occurrence of amputations for diabetic foot ulcer (DFU) patients treated with negative pressure wound therapy (NPWT), as delivered by Vacuum-Assisted Closure Therapy, compared to patients treated with traditional wound therapies (control group) in two different patient populations. METHODS: A retrospective database analysis using administrative data from two different sources was completed. Data sources included: 1) a commercial payor source including 2002-2003 claims and 2) a random 5% sample of 2003 Medicare claims (CMS). ICD-9-CM diagnosis and procedure codes, CPT-4 and HCPCS codes were used to identify NPWT and control patients. Risk adjustment procedures were employed to account for patient acuity differences between the control and NPWT samples. RESULTS: The commercial dataset yielded over 3,500 patients meeting the study criteria while the Medicare dataset included over 12,700 patients. This retrospective analysis demonstrated that the proportion of patients with an amputation was lower following treatment with NPWT when compared to the control group. This finding was consistent for the commercial and Medicare datasets. From the commercial dataset population, NPWT was associated with up to a 34% lower amputation occurrence compared to the control group. (p=0.09) In the Medicare population, the DFU risk-adjusted amputation percentages were 16.6% for control and 10.8% for NPWT groups (p=0.007). Additionally, higher severity patients (categorized based on debridement depth) experienced fewer amputations when treated with NPWT vs. control therapies. CONCLUSIONS: This retrospective analysis is the first to assess the relationship of NPWT to DFU amputations using two large datasets. In this analysis, the results from two distinct datasets consistently suggest that diabetic foot ulcer patients treated with NPWT experienced a lower incidence of amputations compared to control patients. NPWT may play an important role in the incidence of diabetic-related amputation events that lead to significant economic and quality of life implications.