Acute Limb Ischemia (ALI) of the lower limb is defined as a sudden drop in arterial limb perfusion, which is a medical emergency requiring prompt intervention with high amputation and mortality rates in the absence of revascularization. This observational, analytical, and retrospective cohort study with longitudinal follow-up aimed to confirm the relevance of the preoperative inflammatory biomarkers neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the 30-day poor prognosis of patients with Rutherford classification (RC) grades II and III ALI. The ROC analysis found a strong association of an NLR > 4.33 with all studied outcomes, while a PLR > 143.34 was associated with all studied outcomes, except the composite endpoint in all RC stages. Depending on the optimal cut-off value, the ROC analysis found a higher incidence of all adverse outcomes in all high NLR (>4.33) and high PLR (>143.34) groups. A multivariate analysis showed that a high baseline value for NLR and PLR was an independent predictor of amputation (OR:11.09; 95% CI: 5.48–22.42; p < 0.0001; and OR:8.97; 95% CI: 4.44–18.16; p < 0.0001), mortality (OR:22.24; 95% CI: 9.61–51.47; p < 0.0001; and OR:8.32; 95% CI: 3.90–17.73; p < 0.0001), and composite endpoint (OR:21.93; 95% CI: 7.91–60.79; p < 0.0001; and OR:9.98; 95% CI: 3.89–25.55; p < 0.0001), respectively. Furthermore, for all hospitalized patients, the RC grade III (OR:7.33; 95% CI: 3.73–14.26; p < 0.0001) was an independent predictor of amputation (OR:7.33; 95% CI: 3.73–14.26; p < 0.0001), mortality (OR:8.40; 95% CI: 4.08–17.31; p < 0.0001), and composite endpoint (OR: 10.70; 95% CI: 4.48–25.56; p < 0.0001), respectively. The NLR and PLR are excellent predictors of risks associated with ALI for primary and secondary prevention. Our study showed that increased pre-operative values for NLR and PLR are indicators of a poor outcome in patients with RC grades II and III ALI.