Background: The aim of this study was to evaluate surrogate markers commonly used in the literature for diabetic foot osteomyelitis remission after initial treatment for diabetic foot infections. Methods: Thirty-five patients with diabetic foot infections were prospectively enrolled and followed for 12 months. Osteomyelitis was determined from bone culture and histology initially and for recurrence. Chi square and Fischer's exact test were used for dichotomous variables and the student's t-test and Mann-Whitney U test for continuous variables with an alpha of 0.05. Results: Twenty-four patients were diagnosed with osteomyelitis and eleven patients with soft-tissue infections. 16.7% (n=) of patients with osteomyelitis had a re-infection based on bone biopsy. The success of osteomyelitis treatment varied based on the surrogate marker used to define remission: osteomyelitis infection (16.7%), failed wound healing (8.3%), re-ulceration (20.8%), re-admission (16.7%), amputation (12.5%). There was no difference in outcomes among patients who were initially diagnosed with osteomyelitis and soft tissue infections. There were no differences in osteomyelitis re-infection (16.7% vs 45.5%, p=0.07), wounds that failed to heal (8.3% vs 9.1%, p=0.94), re-ulceration (20.8% vs 27.3%, p=0.67), re-admission for diabetic foot infections at the same site (16.7% vs 36.4%, p=0.20), amputation at the same site after discharge (12.5% vs 36.4%, p=0.10). Osteomyelitis at the index site based on bone biopsy indicated that failed therapy was 16.7%. Indirect markers demonstrated a failure rate ranging from 8.3-20.8%. Conclusions: Most osteomyelitis markers were similar to markers in soft tissue infection subjects. Commonly reported surrogate markers were not shown to be specific to identify patients that failed osteomyelitis treatment when compared with patients that had soft tissue infections. Given this, these surrogate markers are not reliable for use in practice to identify osteomyelitis treatment failure.