Background and purpose - An enhanced treatment program may decrease 30-day mortality below 20% after lower extremity amputations (LEA). The potential and limitations for further reduction are unknown. We analyzed postoperative causes of 30-day mortality, and assessed failure to rescue (FTR) rate in LEA patients who followed an enhanced treatment program. Patients and methods - Medical charts of 195 primary LEA procedures were reviewed independently by 3 of the authors, and deaths during hospitalization following amputation were classified according to consensus. Results - 31 patients died within 30 days after surgery. 4 deaths were classified as "definitely unavoidable," 4 as "probably unavoidable," and 23 as "FTR." Patients who died had a higher incidence of sepsis, pneumonia, and acute myocardial infarction compared with those alive. A log binominal regression analysis adjusted for age, sex, ASA score, diabetes, nursing home admission, transfemoral amputation (TFA), and BMI showed that the risk of 30-day mortality was increased for TFA (RR =2.3, 95% CI 1.1-4.8) and for patients with diabetes (RR =2.7, 95% CI 1.3-5.6). The FTR rate (patients with 30-day mortality/all patients with a severe postoperative complication) was 30%. Of the FTR deaths, 20 at some point had active lifesaving care curtailed. Interpretation - Future initiatives should be directed at enhanced sepsis and pneumonia prophylactic actions, in addition to close monitoring of hemodynamics in anemic patients, with the potential to further reduce morbidity and mortality rates.