Background: This retrospective study from a single center in Turkey aimed to compare the surgical results of regional anesthesia and general anesthesia in 203 patients with upper- and lower-extremity amputations.Material/Methods: The study population consisted of patients who underwent extremity amputation between 2017 and 2021. Patients' demographic data, comorbidities, American Society of Anesthesiology (ASA) scores, amputated extremities, causes and extents of amputations, length of hospital stay, associated mortality/morbidity, and postoperative 90-day mortality data were comparatively analyzed between the groups created according to the anesthesia methods used in amputations.Results: The study consisted of 203 patients, of whom 80.8% were male. The most commonly used anesthesia method was peripheral nerve blocks (32.5%), followed by spinal anesthesia (31.5%), general anesthesia (31.0%), epidural anesthesia (2.0%), combined spinal-epidural anesthesia (1.5%), and sedo-analgesia (1.5%). Of the amputations performed, 37.0% were upper-extremity and 63.0% were lower-extremity. Peripheral nerve blocks were used most frequently in upper-extremity amputations (71.5%), and spinal anesthesia was used most frequently in lower-extremity amputations (48.9%). The mean length of hospital stay of the patients who underwent surgery under regional anesthesia methods was shorter than that of those who underwent general anesthesia (8.7 +/- 7.4 days vs 15.0 +/- 20.6 days). The mortality rate was 0.5% in the first 24 h, 0.5% in the next 48 h, and 4.9% in total.Conclusions: The study findings demonstrated that performing extremity amputations under regional anesthesia techniques, particularly peripheral nerve blocks, reduces mortality/morbidity, the need for postoperative intensive care, mean length of stay in hospital, and hospital costs.