The purpose of this study was to analyze the outcomes of major lower extremity amputations (MLEAs) in a series, including diabetic patients, with the aim to study whether diabetes mellitus is a risk factor of in-hospital mortality and perioperative complications. A retrospective analysis of 283 MLEAs (221 of these patients were diabetic and 62 were nondiabetic) performed between January 1, 1998, and December 31, 2008, at the General Surgery Department and Diabetic Foot Unit of La Paloma Hospital in Las Palmas de Gran Canaria (Canary Islands) was done. The significant risk factors of mortality were >" xbd="324" xhg="301" ybd="1481" yhg="1446"/>75 years of age (odds ratio [OR] = 4.1, 95% confidence interval [CI] = 1.4-11.7), postoperative cardiac complications (OR = 12.3, 95% CI = 3.7-40.2) and postoperative respiratory complications (OR = 3.8, 95% CI = 1.0-13.3). No statistically significant risk factors were found related to the presence of systemic and wound-related complications. In diabetic patients, the significant risk factors of mortality were postoperative cardiological complications (OR = 13.6, 95% CI = 3.1-59.6), postoperative respiratory complications (OR = 5.9, 95% CI = 1.0-35.5), and first episode of amputation (OR = 5.9, 95% CI = 1.4-24.3). There were no statistically significant differences in the outcome of major amputations between diabetic and nondiabetic patients. Hospital stay was significantly longer in diabetic patients (P < .01) though when the patients with diabetic foot infections were excluded, this difference was not found.