OBJECTIVES: To evaluate resource utilization and direct costs of care for patients treated with negative pressure wound therapy (NPWT) compared to standard moist wound therapy (MWT) in the treatment of partial diabetic foot amputation wounds. METHODS: 162 diabetic subjects with post-amputation ulcers were enrolled into a sixteen-week, randomized clinical trial. Patients randomized to NPWT (n=77) received therapy with dressing changes every 48h. Control patients (n=85) received standard MWT according to consensus guidelines. Resource utilization and procedures were analyzed using a standardized protocol. RESULTS: More surgical procedures were performed in the MWT group versus the NPWT group (120 vs. 43, p<0.001). The average number of dressing changes performed per patient was 118.0 (range 12-226) for MWT compared with 41 (range 6-140) for NPWT (p=0.0001). The MWT group had an average of 11 (range 0-106) outpatient treatment visits during the study period compared with 4 (range 0-47) in the NPWT group (p<0.05). The average total direct cost per patient treated for 8 weeks or longer (independent of clinical outcome) was $27,270 and $36,096 in the NPWT and MWT group, respectively (incremental cost difference =$8,826). Proportionally, the highest costs were related to inpatient stay, antibiotics and wound dressing treatment (materials and staff). The average total cost to achieve healing was $25,954 for NPWT patients (N=43) compared with $38,806 for the MWT (n=33) group (incremental difference = $12,852). CONCLUSION: Treatment of diabetic wounds using NPWT compared to MWT was associated with substantially lower resource utilization with regard to outpatient visits, dressing changes, and surgical procedures. Overall direct treatment costs were also substantially different as treatment costs with NPWT were on average $8,800 less than with MWT. In summary, this study revealed treatment with NPWT resulted in a greater proportion of patients obtaining wound healing at a lower overall cost of care.