Purpose Risk factors for wound complications or 30-day mortality after major amputation in patients with peripheral arterial disease remain unclear. We investigated the outcomes of major amputation in patients with peripheral arterial disease. Methods Patients who underwent major amputation from 2008 to 2015 were retrospectively analyzed. The main outcome measures were risk factors for wound complications and 30-day mortality after major lower limb amputations. Major amputation was defined as above-knee amputation or below-knee amputation. Wound complications were defined as surgical site infection or wound dehiscence. Results In total, 106 consecutive patients underwent major amputation. The average age was 77.3 ± 11.2 years, 67.9% of patients had diabetes mellitus and 35.8% were undergoing hemodialysis. Patients who underwent primary amputation constituted 61.9% of the cohort, and the proportions of above-knee amputation and below-knee amputation were 66.9% and 33.1%, respectively. The wound complication rate was 13.3% overall, 10.3% in above-knee amputation, and 19.5% in below-knee amputation. Multivariate analysis showed that the risk factors for wound complications were female sex (hazard ratio, 4.66; 95% confidence interval, 1.40-17.3; P = 0.01) and below-knee amputation (hazard ratio, 4.36; 95% confidence interval, 1.20-17.6; P = 0.03). The 30-day mortality rate was 7.6%, pneumonia comprised the most frequent cause of 30-day mortality, followed by sepsis and cardiac death. Multivariate analysis showed that a low serum albumin concentration (hazard ratio, 3.87; 95% confidence interval, 1.12-16.3; P = 0.03) was a risk factor for 30-day mortality. Conclusions Female sex and below-knee amputation were risk factors for wound complications. A low serum albumin concentration was a risk factor for 30-day mortality after major amputation in Japanese patients with peripheral arterial disease.