BackgroundTransmetatarsal amputation (TMA) is a commonly performed procedure for gangrene in the setting of diabetes or peripheral vascular disease. The purpose of this study is to investigate the incidence of and risk factors for reoperation and perioperative complications after TMA in patients undergoing surgery for primarily infectious/diabetic wounds versus peripheral vascular disease. MethodsPatients undergoing TMA between January 1, 2015 and December 31, 2020 were identified using the American College of Surgeons National Surgical Quality Improvement Program database. The indication for surgery was reported using the International Classification of Disease 9/10 codes. Patients were categorized into two groups: patients undergoing surgery for primarily infectious/diabetic wounds versus peripheral vascular disease. The incidence of 30-day mortality, readmission, reoperation, nonhome discharge, and various medical and surgical complications was reported. Outcome measures were compared between the diabetic and peripheral vascular disease groups. Logistic regression was used to identify independent risk factors for each outcome measure of interest. Results3392 patients were included in the final cohort. There was a 30-day mortality rate of 2.9%, reoperation rate of 13.8%, readmission rate of 16.8%, surgical complication rate of 22.2%, and medical complication rate of 15.8%. Patients undergoing surgery for a vascular indication had a higher rate of mortality, reoperation, hospital readmission, nonhome discharge, and various medical complications (p < 0.05). Patients undergoing surgery for infectious/diabetic wounds had a higher rate of deep surgical site infection and systemic sepsis (p < 0.05). A vascular surgical indication was independently associated with reoperation and overall medical complications (p < 0.05). Various factors, including age, body mass index, medical comorbidities, and the presence of preoperative sepsis were associated with poor outcomes. ConclusionSignificant rates of mortality, reoperation, and hospital readmission were reported after TMA. The presence of peripheral vascular disease was independently associated with reoperation and medical complications. Patients undergoing TMA, particularly for peripheral vascular disease, should be counseled about perioperative risks and indicated for surgery carefully.