DFU is associated with prolonged hospital stay and high mortality. Very few data have been reported the hypothetical gender differences in relation to the different clinical factors playing a role in patient’s outcomes. We aimed to identify clinical variables that significantly characterize diabetic patients hospitalized for DFU in relation to gender and clinical DFU-related principal factors, cardiovascular and peripheral vascular disease. 500 diabetic patients, mean age 64.8±12 years old, 153 females and 347 males, with a diagnosis of diabetic foot complications hospitalized in 2008-2022 were selected. For all patients we considered clinical general and DFU parameters, outcomes in terms of amputation and revascularization rate, precedent MACE, kidney disease prevalence. The duration of diabetes was 19.3±4.3 yrs. in the entire group and longer in females than males (21.2±11.7 yrs. and 18.4±11.7, respectively; p=0.008). A decrease in eGFR (calculated with EPI-CKD formula) was found in females (66.1±29.9 ml/min) compared to males (74.6±31) (p=0.003). Although 78.6% of patients were treated with hypolipidemic therapy, females showed higher values of cholesterol (151.3±35.3) than males (143.1± 39.8 mmol/L) (p=0.03). Current smoking was found in 29% of total cohort and 20.9% in females in comparison with 32% in males (p=0.001). CKD was described as mild in 322 out of 500 patients (64.4%), as moderate in 119 (23.8%) and severe in 59 (11.8%); a significantly higher prevalence of moderate CKD was detected in females (36.6%) in comparison to males (18.2%) (p<0.001). Hypertension was detected in 416 patients (83.2%) and slightly higher in females (136 out of 153, 88.9%) compared to males (280 out of 347, 80.7%) (p=0.033).When we considered MACE in the entire cohort studied, we found IMA in 160 out of 500 patients (32%), stroke in 20 (4%) and cardiac insufficiency in 1 (0.2%); only prevalence of stroke was higher in females (12, 7.8%) than in males (8, 2.3%) (p=0.002). The multivariate analysis confirmed a significantly higher prevalence of stroke (OR 0.22, CI 0.07,p=0.005) and moderate chronic kidney disease (OR 0.34, CI 0.15, p=0.008), higher values of total cholesterol (OR 0.99, CI 0.99 p=0.009) in females and a higher prevalence of smoking in males (OR 2.26. CI 1.37, p=0.001). A 15 years-DFU cohort of diabetic patients is characterized by gender differences evidencing a minor prevalence of DFU and a major complexity in CV and kidney disease in diabetic females.