OBJECTIVE: We sought to evaluate the use of oligonucleotide arrays to discriminate colonization from infection due to Staphylococcus aureus in diabetic foot ulcers. RESEARCH DESIGN AND METHODS: We included diabetic patients hospitalized in a diabetic foot department for an episode of foot ulcer. Only patients who had no antibiotic treatment during the previous 6 months were included. At admission, ulcers were classified on clinical examination, according to the Infectious Diseases Society of America system. Seventy-two patients with a culture positive only for S. aureus as the sole pathogen were included. In individuals with a grade 1 ulcer, a second wound bacterial specimen was obtained 1 month later. Using oligonucleotide arrays, S. aureus resistance and virulence genes were compared between grade 1 and grades 2-4 ulcers. RESULTS: S. aureus was initially isolated from 22 grade 1 and 50 grade 2-4 ulcers: 35 were methicillin resistant and 37 methicillin sensitive. In 20 grade 1 ulcers (92%), no virulence genes were identified, whereas these genes were present in all but 1 grade 2-4 ulcers. During follow-up, the two grade 1 ulcers that were infected with strains carrying virulence genes rapidly deteriorated; the array technology showed unchanged genotype profiles. On the contrary, two grade 1 ulcers healed: the genotype profiles were different from those at inclusion but without appearance of virulence genes. CONCLUSIONS: The DNA array appears as a promising technique and is easy to perform. Our observational study suggests that it might help distinguish colonized grade 1 from infected grade 2 wounds, predict ulcer outcome, and contribute to a more adequate use of antibiotics.