Background: Diabetic Foot Disease (DFD) is more prevalent among males and is associatedwith an excess risk of cardiovascular events or mortality. Aims: This study aimed at exploring the risk of cardiovascular events, renal failure, and all-causemortality after incident DFD hospitalizations, separately in males and females, to detect any genderdifference in a cohort of 322,140 people with diabetes retrospectively followed up through administrativedata sources in Tuscany, Italy, over the years 2011-2018. Methods: The Hazard Ratio (HR) for incident adverse outcomes after first hospitalizations forDFD, categorized as major/minor amputations (No.=449;3.89%), lower limbs revascularizations(LLR: No.=2854;24.75%), and lower-extremity-arterial-disease (LEAD) with no procedures(LEAD-no proc: No.=6282;54.49%), was compared to the risk of patients having a background ofDFD (ulcers, infections, Charcot-neuroarthropathy: No.=1,944;16.86%). Results: DFD incidence rate was higher among males compared to females (1.57(95%CI:1.54-1.61) vs. 0.97(0.94-1.00)/100,000p-years]. After DFD, the overall risk of coronary arterydisease was significantly associated with the male gender and of stroke with the female gender.LEAD-no proc and LLR were associated with the risk of stroke only in females, whereas they werefound to be associated with the risk of coronary artery disease among females to a significantlygreater extent compared to males. The incident of renal failure was not associated with any DFDcategory. Amputations and LEAD-no proc significantly predicted high mortality risk only in females,while LLR showed reduced risk in both genders. Moreover, females had a greater risk ofcomposite outcomes (death or cardiovascular events). Compared to the background of DFD, therisk was found to be 34% higher after amputations (HR: 1.34(1.04-1.72)) and 10% higher afterLEAD-no proc (HR:1.10(1.03-1.18)), confirming that after incident DFD associated with vascularpathogenesis, females are at an increased risk of adverse events. Conclusion: After incident DFD hospitalizations, females with DFD associated with amputationsor arterial disease are at a greater risk of subsequent adverse cardiovascular events than those witha DFD background.