Abstract Acute limb ischemia (ALI) and chronic limb-threatening ischemia (CLTI) are severe vascular conditions that can be lethal. The inflammatory response in these diseases, characterized by increased levels of neutrophils and platelets, highlights the importance of prompt management. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a useful biomarker during the COVID-19 pandemic and high NLR levels were found to be associated with an increased risk of ALI and other thromboembolic events. The aim of this systematic review was to analyze the prognostic role of the NLR regarding the risk of amputation and mortality in patients diagnosed with ALI and CLTI. We included 12 studies (five for ALI, with 1,145 patients, and seven for CLTI, with 1,838 patients), following the PRISMA guidelines. Treatment results were evaluated, including amputation and mortality. We found that high NLR values were consistently associated with an increased risk of amputation and/or mortality, with pooled odds ratios ranging from 1.28 to 11.09 in patients with ALI and from 1.97 to 5.6 in patients with CLTI. The results suggest that NLR may represent an important tool for informed decision-making in the management of these patients.