OBJECTIVES: To assess the impact of diabetes on direct medical expenditures for visits and prescribed medications related to skin and soft tissue infections (SSTIs). METHODS: Hospital inpatient, outpatient, office, and emergency room visits and prescribed medications related to SSTIs were identified from the 2010 and 2011 Medical Expenditure Panel Survey. Total SSTI costs per patient per year were calculated by summing overall costs of all SSTI medical events. Differences in mean and median SSTI costs between patients with and without diabetes were assessed with the Wilcoxon-Mann-Whitney and median two-sample tests.  RESULTS: We identified 1684 SSTI events from 438 patients, including 93 (21%) having diabetes. Events (761 to 923) and costs ($259,784.74 to $375,696.03) increased from 2010 to 2011. Patients with diabetes were older (61 vs. 47) and a greater percentage had public insurance (46% vs. 28%). Average SSTI costs per patient with diabetes in 2010 and 2011 were: $135.84 (standard deviation [sd]= 259.72) and $873.59 (sd=2275.98) for prescribed medicines, $8990.54 (sd=9506.02) and $8590.86 (sd=8685.70) for inpatient and emergency room, $706.61 (sd=1729.25) and $1255.25 (sd=3561.37) for outpatient and office. Average SSTI costs per patient without diabetes in 2010 and 2011 were: $143.91 (standard deviation [sd]= 411.68) and $46.71 (sd=78.07) for prescribed medicines, $832.92 (sd=1482.56) and $2431.65 (sd=7758.02) for inpatient and emergency room, $486.55 (sd=1237.81) and $568.32 (sd=1247.08) for outpatient and office. The mean total SSTI cost difference between patients with and without diabetes was $1627.93 ($2481.09-$853.16, p-value=0.1441) in 2010 and $1065.60 ($2604.75-$1539.15, p-value=0.1789) in 2011. The median total SSTI cost difference per patient per year was $78.61 ($237.72-$159.11, p-value=0.3948) and $38.21 ($237.00-$198.79, p-value=0.2666).  CONCLUSIONS: In a nationally representative sample, mean and median SSTI costs related to medical visits and prescriptions were higher among patients with diabetes, however these costs did not differ significantly compared to patients without diabetes.