Osteomyelitis complicates 20% of patients with infected diabetic foot ulcers. In this study, two strategies for treating pedal osteomyelitis were compared in a pilot study.This was a retrospective, non-randomized, single center 2 arm cohort study, conducted between 2020-2022 involving 53 patients at a tertiary limb salvage unit. All patients were managed with debridement and proximal bone biopsy. Group A was treated with systemic antibiotics for up to 6 weeks. Group B had vancomycin or gentamycin eluting bone void filler implanted into the diseased bone medullary cavity(s) and 1 week of oral antibiotics. Patients were followed independently for the primary endpoint of osteomyelitis treatment failure and secondary endpoints of amputation free survival, wound healing, minor amputation, and treatment-limiting side-effects.Survival analysis demonstrated no significant difference in treatment failure (p=0.35) or amputation free survival (p=0.46). Limb salvage rates were 88% in Group A and 89% in Group B. Wounds healed in 85% in Group A and 89% in Group B. Minor amputations occurred in 21% in Group A and 11% in Group B. Treatment limiting side effects occurred in 6% in Group A and were absent in Group B.In conclusion, the use of antibiotic eluting bone void filler appeared safe without extended systemic antibiotics in this study. Group B had fewer intravenous lines, requirement for home nursing, and treatment limiting side effects. A larger randomized controlled trial examining longer term clinical and radiological efficacy, treatment costs and side effects is warranted. Level of Clinical EvidenceThis is a retrospective cohort study, therefore the level of clinical evidence is 2.