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Background Intraoperative transfusions in vascular patients undergoing major lower limb amputations (LLAs) are associated with worse postoperative outcomes. Methods We conducted a retrospective study from 2015 to 2020 to identify perioperative factors associated with the need for intraoperative transfusion for patients undergoing below knee or above knee amputations secondary to vascular disease. Results A total of 65 patients with major LLAs were identified, 39 (60%) with below knee and 26 (40%) with above knee amputations. There were 15 (23%) patients who were transfused intraoperatively and 50 (77%) who were not. Six (15%) of the below knee patients and 9 (34%) of the above knee patients required intraoperative transfusion. Of the variables studied, only preoperative hemoglobin (8.6 ± .4 vs 9.9 ± .2 g/dL, P = .01), change in hemoglobin (−.1 ± .4 vs .8 ± .2 g/dL, P = .01), estimated intraoperative blood loss (416 ± 168 vs 126 ± 14 mL, P = .04), and operative duration (116 ± 19 min. vs 89 ± 6 min, P = .046) were associated with a transfusion requirement with these patients having a longer length of stay (42 [13-76] vs 21 [12-31] days, P = .04) and a higher risk of mortality (33% vs 10%, P = .03). Discussion The study is limited by a small sample size from a single institution. However, patients who received an intraoperative transfusion had a lower starting hemoglobin, higher estimated blood loss, required longer hospital stays, and were at a higher risk for post-discharge mortality.