Purpose: Elevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with poor outcomes in various diseases. The objectives of this study were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with diabetic foot ulcers (DFU) undergoing amputations. Patients and Methods: A retrospective observational study was performed that included a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause death. According to the PLR and NLR cut-off values, patients were divided into two groups and Kaplan-Meier survival curves were constructed. Multivariable Cox regression was conducted to test the independent predictors of mortality in the study cohort. Results: All-cause mortality was significantly higher in patients with a high PLR/NLR compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS) rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively (p=0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were 85.2%, 58.6% and 23.9% (p<0.001). According to the multivariate analysis, age (HR 1.074, 95% CI 1.045-1.104, p<0.001), Wagner classification (HR 2.274, 95% CI 1.351-3.828, p=0.002), PLR (HR 1.794, 95% CI 1.014-3.174, p=0.045), NLR (HR 2.029, 95% CI 1.177-3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001-1.004, p<0.001) and direct bilirubin (HR 1.154, 95% CI 1.081-1.232, p<0.001) were independent predictors of mortality following amputation. Conclusion: Postoperative PLR and NLR values may be reliable predictive biomarkers of mortality in patients following amputation for DFU. Considering the high mortality in those patients, the patients with elevated PLR/NLR should be given more intensive in clinical practice.