Introduction: Diabetic foot osteomyelitis (DFO) is a common complication in patients with diabetic foot ulcers. Bone infection increases the risk of amputation and hospitalization, being a current challenge for clinicians involved in the field. Nonetheless, there are poor data about the role of peripheral arterial disease (PAD) in subjects with DFO. Accordingly, the current study aimed to evaluate the outcomes of patients with DFO, comparing patients with and without PAD. Methods: The study is a prospective study including a population of patients affected by DFO located in the forefoot. All patients were managed by a surgical conservative approach defined by the removal of the infected bone in association to the antibiotic therapy based on each specific clinical case. Patients were divided into two groups: those with PAD (ischaemic-DFO) and those without (neuropathic-DFO). After 1 year of follow-up, the following outcomes were evaluated and compared between groups: healing, healing time, minor amputation, major amputation, hospitalization, need for surgical re-intervention. Results and Discussion: One hundred sixty-six patients were included, 87 (52.4%) of them had ischaemic-DFO and 79 (47.6%) neuropathic-DFO. Patients with ischaemic-DFO in comparison to neuropathic-DFO were older (72.5±9 vs 64.1±15.5 years, p<0.0001), had longer diabetes duration (21.8±5.6 vs 16.4±7.6 years, p<0.0001), higher rate of dialysis (13.8 vs 1.3%, p=0.001) and ischaemic heart disease (79.3 vs 12.7%, p<0.0001). The outcomes for ischaemic-DFO and neuropathic-DFO were: healing (96.5 vs 97.5%, p=0.7), healing time (7.8±6.2 vs 5.7±3.7 weeks, p=0.01), minor amputation (16.1 vs 3.8%, p=0.006), major amputation (0 vs 0%, ns), hospitalization (69 vs 51.9%, p=0.02), surgical re-intervention (14.9 vs 8.8%, p=0.004) respectively. At the multivariate analysis, PAD resulted an independent predictor of minor amputation (in association with presence of gangrene), hospitalization (in association with systemic infection), and surgical re-intervention. Conclusions: Ischaemic-DFOs were characterized by longer healing time, more cases of minor amputation, hospitalization, and surgical re-intervention in comparison to neuropathic-DFOs. PAD independently increased the severity of DFO.