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Background: Poor nutritional status is common among patients undergoing lower extremity amputation (LEA). In this study, the association between preoperative hypoalbuminemia, a marker for malnutrition, and postoperative mortality in patients undergoing LEA was explored., Methods: Data on patients undergoing LEA between 2005 and 2017 were retrospectively analyzed from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into clinically relevant categories based on their serum albumin level (<2.5, 2.5-3.39, ≥3.4 g/dl) and were further stratified according to amputation level. Operative death was compared across groups and multivariable logistic regression was performed to estimate risk-adjusted odds ratio (AOR)., Results: In 35,383 patients, the rate of 30-day postoperative mortality was 7.6% (n = 2693). Mortality rate was highest in patients with very low albumin levels (11%) as compared to low (6.8%) and normal levels (3.9%). On multivariable analysis, lower albumin levels emerged as a risk-adjusted independent predictor of mortality. After risk-adjustment, patients with very low albumin levels (AOR [95% CI]: 2.25 [1.969-2.56], P < 0.001) and low albumin levels (AOR [95% CI]: 1.42 [1.239-1.616], P < 0.001) had higher odds of mortality when compared to patients with normal albumin levels. On sensitivity analysis, a similar trend was seen in patients undergoing above knee amputation but not in patients undergoing minor amputations., Conclusions: In patients undergoing major LEA, hypoalbuminemia is associated with an increased risk of postoperative mortality in a dose response manner, specifically in above knee amputations. Monitoring and optimizing patients' nutritional status before surgery, when possible, may be warranted and should be further explored., (Copyright © 2021 Elsevier Inc. All rights reserved.)