OBJECTIVES: Critical limb ischemia (CLI) is a severe complication of peripheral artery disease (PAD). Many CLI patients receive a lower extremity amputation (LEA) as a first line treatment. Limb salvage programs provide an alternative treatment pathway aimed at the prevention of LEAs. The objective of this analysis was to estimate the potential lifetime economic savings to a national payer from the implementation of a limb salvage program in the United States (US). METHODS:  A simulation model was developed in MS Excel to estimate the direct healthcare cost of implementing a limb salvage program in the US for all CLI patients. The model was from the perspective of Centers for Medicare & Medicaid Services (CMS). Clinical endpoints were the number of amputations and the LEA reduction rate associated with a limb salvage program. Cost parameters included lifetime amputation burden and limb salvage program cost estimates. All parameter values were obtained from the published literature and adjusted to 2015 dollars using the Medical Care Component of the Consumer Price Index. RESULTS:  LEAs have been reported at 73,000 annually. The estimated lifetime direct healthcare cost for an amputee patient is $640,849. When aggregated, the expected lifetime cost is estimated at $46.7 billion. In the published literature, comprehensive limb salvage programs are shown to reduce the rate of amputations from 36% to 86%. Using the midpoint of this reduction (61%) and accounting for the estimated cost of a limb salvage program ($1.7 billion) yields a cost savings of $26.8 billion. The reduction in amputations from a formal limb salvage program is expected to save CMS from $15.2 billion assuming a 36% salvage rate to $38.5 billion assuming an 86% salvage rate. CONCLUSIONS:  The lifetime economic burden of amputees is substantial. A national limb salvage program may reduce this burden by $15.2 to $38.5 billion.