Aim: To evaluate the incidence of MRSA infection, re-infection, and the conversion of non-MRSA bacterial pathogens to MRSA in re-infections. Methods: This was a post hoc analysis of 233 patients that participated in an RCT for moderate and severe diabetic foot infections with 12-month outcomes. We used bone culture and/or pathology to define osteomyelitis (OM). Soft tissue infections (STI) were defined based on negative bone biopsy or negative MRI. Moderate and severe infection was based on criteria of the International. Working Group on the Diabetic Foot infection classification. All subjects required surgery. We evaluated bacterial pathogens from bone and deep soft tissue from their initial infection and when there was re-infection. We defined conversion when a subject did not have MRSA in either their first OM or STI culture and had MRSA when there was re-infection. We used χ2 for comparison of clinical events, with alpha of <0.05. Results: OM was present in 73.0% (n=170) of cases. MRSA incidence was 8.6% (n=20), with no difference between STI and OM (14.3% vs. 6.5%, p=0.06). Reinfection occurred in 29.2% (n=68), with no difference between STI and OM (36.5% vs. 26.5%, p=0.14). MRSA was seen in 29.4% (n=20) of the reinfections, with no difference between STI and OM (13.0% vs. 28.9%, p=0.16). Conversion to MRSA was seen in 14.7% (n=10), with no difference between STI and OM (4.3% vs. 20%, p=0.12). MRSA was 4.4 times more likely in re-infection compared to index infections (29.4% vs 8.6%, CI 2.2-8.9, p<0.01). Conclusion: The incidence of MRSA is 4.4-fold higher after re-infection. The incidence of MRSA for the first infection (8.6%) was low. Re-infection with MRSA (29.4%) and conversion to MRSA (14.7%) were common. There was no difference seen in the incidence rates for reinfection, MRSA, reinfection with MRSA, and conversion to MRSA between patients with STI and OM. Disclosure M.A.Suludere: None. A.L.Killeen: Research Support; 3M/KCI, AstraZeneca, BioTissue surgical, Hologenix, LLC, Integra LifeSciences, Kent Imaging Inc., Microbion, PolarityTE, Inc., Smith+Nephew, Stark Enterprises, LLC, Xyken, VasoActiv, ViOptix. P.Crisologo: None. L.A.Lavery: Research Support; AstraZeneca, Tissue tech, American Diabetes Association, PolarityTE, Inc., Microbion, Jarvis, Integra Lifesciences Holdings Corp, Smith+Nephew.