OBJECTIVE: To determine risk factors, microbiology, and prognosis of diabetic foot osteomyelitis (DFO). METHODS: We conducted a retrospective cohort study of 456 persons diagnosed with diabetic foot disease admitted to a grade-A tertiary hospital from January 2012 to December 2022. Multifactorial Cox regression was used to analyze independent risk factors for DFO. Medical records were reviewed to determine etiologic agents and antibiotic susceptibility profiles. In addition, 5-year survival rates of all DFO patients and those undergoing amputation were analyzed using Kaplan-Meier curves. RESULTS: Multivariate Cox regression identified higher Wagner grades (hazard ratio 3.17, 95% confidence interval 2.04, 4.94) as independent risk factors for DFO. In the DFO group, a total of 62 patients had positive bone or deep tissue cultures. The most prevalent Gram-positive bacterial isolates were Staphylococcus aureus (11.29%) and Enterococcus faecalis (11.29%), while Gram-negative infections were caused most often by Proteus vulgaris (4.84%). Polymicrobial infections were common (27.41%). Five-year survival rates were lower among DFO patients than in matched DF controls, and lower among major amputation than minor amputation and nonamputation DFO patients. CONCLUSIONS: Higher Wagner grades were independent risk factors for DFO. Major amputation does not improve 5-year survival rates in DFO patients.