Background The aim of this study was to examine the relationship between patient education level and 5-year mortality after major lower extremity amputation. Methods The records of all patients who underwent above-knee or below-knee amputation at the Nashville Veterans Affairs Medical Center by the vascular surgery service between January 2000 and August 2006 were retrospectively reviewed. Formal levels of education of the study patients were recorded. Outcomes were compared between those patients who had completed high school and those who had not. Bivariate analysis using χ 2 and Student's t tests and multivariate logistic regression were performed. Results Five-year mortality for patients who had completed high school was lower than for those who had not completed high school (62.6% vs 84.3%, P = .001), even after adjusting for important clinical factors (odds ratio for death, .377; 95% confidence interval, .164–.868; P = .022). Conclusion Patients with less education have increased long-term mortality after lower extremity amputation.