Background: Penetrating vascular injuries (PVIs) of the lower limbs due to stab wounds are associated with high mortality and limb loss rates. We analyzed the outcomes of a series of patients who underwent surgical treatment of these lesions, assessing the presence of any factor associated with limb loss and mortality; (2) Methods: Data of patients admitted from 01/2008 to 12/2018 were retrospectively analyzed. Primary outcomes were the limb loss and the mortality rate at 30 days postoperatively. Univariate and multivariate analyses were performed as appropriate.pvalues < 0.05 were considered significant; (3) Results: Data of 67 male patients were analyzed. Two died (3%) and three (4.5%) had a lower limb amputation after failed revascularization. In the univariate analysis, the clinical presentation significantly affected the risk of postoperative mortality and limb loss. The location of the lesion at the superficial femoral artery (OR 4.32,p= 0.001) or at the popliteal artery (OR 4.89,p= 0.0015) also increased the risk. In the multivariate analysis, the need for a vein graft bypass was the only significant predictor of limb loss and mortality (OR 4.58,p< 0.0001); (4) Conclusions: PVIs of lower limbs due to stab wounds were lethal in 3% of cases and lead to a secondary major amputation in 4.5% more cases. The need for a vein bypass grafting was the strongest predictor of postoperative limb loss and mortality.