OBJECTIVES: The aim of this study is to calculate direct cost of management diabetic foot infection (DFI) due to MRSA in diabetes mellitus (DM) patient-population treated with linezolid and to identify the most important factors related to treatment costs. METHODS: A cost-study was performed with data from 70 prospectively patients with DFI treated with linezolid from-2006-to-2008 in 10 Spanish Hospitals included in a non-comparative clinical trial. Cost for in-patient-stay, and outpatient management were calculated retrospectively from diagnosis until healing or death in those patients where the cost data could be estimated. Cost for linezolid treatment (IV-oral), IV administration and monitoring were also estimated. Resource utilization not collected during the study was based on published literature. Cost data derived from literature and Spanish database. Mean values for each item were used to calculate cost average. All costs are expressed in Euros 2007. RESULTS: Mean age was 63.2 years old (SD 13.0), being 68.1% males. Duration of DM was 16.5 years. A total of 55 patients healed without amputation (78.6%) and 9 (12.9%) healed after amputation. Total cost for a patient without amputation was €9429.7 (95% CI 8404.2-10455.3), while corresponding cost for a patient with amputation was €9949.9 (95% CI 6034.3-13865.6). Hospitalization accounts for 54% of cost of treating DFI in patients without amputation and 48% in patients with amputation. Surgery cost was 17% of total cost in patients undergoing amputation. Drug costs didn’t account for the major part of costs incurred during in-patient phase. Outpatient costs were 5% and 7% of total cost in patients without and with amputation, respectively. CONCLUSIONS: : These are the first cost data results for DFI due to MRSA in Spain. Amputations were associated with high cost mainly due to surgery and long-term cost. These findings suggest the potential efficiency of a targeted approach program to prevent amputations in patients with DFI.