The aim of the current study was to evaluate the outcomes of patients with diabetic foot osteomyelitis (DFO), comparing subjects with and without peripheral arterial disease (PAD). The study is a prospective study including a population of patients affected by a DFO located in the forefoot. All patients were managed by a surgical conservative approach defined by the removal of the infected bone, in association with the antibiotic therapy. Patients were divided into two groups: those with PAD (neuro-ischaemic DFO) and those without (neuropathic DFO). After 1 year of follow-up, the following outcome were evaluated and compared between groups: healing, healing time, minor amputation, major amputation, hospitalization, need for surgical re-intervention. Overall, 166 patients were included, 87(52.4%) of them had neuro-ischaemic DFO and 79 (47.6%) neuropathic DFO. Patients with neuro-ischaemic DFO in comparison to neuropathic DFO were older (72.5 ± 9 vs 64.1 ± 15.5 years,  < .0001), had longer diabetes duration (21.8 ± 5.6 vs 16.4 ± 7.6 years,  < .0001), higher rate of dialysis (13.8 vs 1.3%,  = .001) and ischaemic heart disease (79.3 vs 12.7%,  < .0001). Outcomes for neuro-ischaemic DFO and neuropathic DFO were: healing (96.5 vs 97.5%,  = .7), healing time (7.8 ± 6.2 vs 5.7 ± 3.7 weeks,  = .01), minor amputation (16.1 vs 3.8%,  = .006), major amputation (0 vs 0%, ns), hospitalization (90.8 vs 51.9%,  < .0001), surgical re-intervention (14.9 vs 8.8%,  = .004) respectively. In addition, PAD resulted in an independent predictor of minor amputation, hospitalization, and surgical re-intervention. DFO in patients with PAD was characterized by longer healing time, more cases of minor amputation, hospitalization, and surgical re-intervention. PAD independently predicted the risk of minor amputation, hospitalization, and surgical re-intervention, while it was not associated with the healing rate.