ABSTRACT: Lower extremity amputation is often performed in patients where both lower extremities are at risk due to peripheral arterial disease or diabetes, yet the proportion of patients who progress to amputation of their contralateral limb is not well defined. We sought to determine the rate of subsequent amputation on both the ipsilateral and contralateral lower extremities following initial amputation.We conducted a retrospective review of all patients undergoing lower extremity amputation (exclusive of trauma or tumor) at our institution from 1998 to 2010. We used International Classification of Diseases-Ninth Revision codes to identify patients and procedures as well as comorbidities. Outcomes included the proportion of patients at 1 and 5 years undergoing contralateral and ipsilateral major and minor amputation stratified by initial major vs minor amputation. Cox proportional hazards regression analysis was performed to determine predictors of major contralateral amputation.We identified 1715 patients. Mean age was 67.2 years, 63% were male, 77% were diabetic, and 34% underwent an initial major amputation. After major amputation, 5.7% and 11.5% have a contralateral major amputation at 1 and 5 years, respectively. After minor amputation, 3.2% and 8.4% have a contralateral major amputation at 1 and 5 years while 10.5% and 14.2% have an ipsilateral major amputation at 1 and 5 years, respectively. Cox proportional hazards regression analysis revealed end-stage renal disease (hazard ratio [HR], 3.9; 95% confidence interval [CI], 2.3-6.5), chronic renal insufficiency (HR, 2.2; 95% CI, 1.5-3.3), atherosclerosis without diabetic neuropathy (HR, 2.9; 95% CI, 1.5-5.7), atherosclerosis with diabetic neuropathy (HR, 9.1; 95% CI, 3.7-22.5), and initial major amputation (HR, 1.8; 95% CI, 1.3-2.6) were independently predictive of subsequent contralateral major amputation.Rates of contralateral limb amputation are high and predicted by renal disease, atherosclerosis, and atherosclerosis with diabetic neuropathy. Physicians and patients should be alert to the high risk of subsequent amputation in the contralateral leg. All patients, but particularly those at increased risk, should undergo close surveillance and counseling to help prevent subsequent amputations in their contralateral lower extremity.