OBJECTIVES:  The most advanced form of peripheral artery disease (PAD) is critical limb ischemia (CLI), defined as chronic ischemic rest pain, ulcers, or gangrene attributable to arterial occlusive disease. This research estimates the risk of major amputation or inpatient death by treatment pathway for patients with CLI. For those patients having a major amputation the incremental expenditures per member per month (PMPM) were estimated. METHODS: Data from MarketScan Commercial and Medicare Supplemental Databases from January 2006-December 2014 was utilized. Eligible patients required at least 2 visits—one with an ICD-9 diagnosis of PAD and another of CLI, as well as 6 months of continuous enrollment prior to diagnosis of CLI. Cohorts were developed based on patients’ treatment pathway: endovascular revascularization (EVAS), surgical revascularization (SVAS), minor amputation without revascularization (MinAMP), or no intervention (NONE). The odds of major amputation or inpatient death for each cohort were estimated using the Cox proportional hazards model. Total expenditures PMPM (inpatient and outpatient) were estimated using a gamma log-link model. All models were adjusted for patient demographics and comorbidities. RESULTS: Patients who met inclusion criteria (N=52,527), were subset into treatment pathway cohorts: EVAS (N=29,798), SVAS (N=10,683), MinAMP (N=5,126), NONE (N=6,920). Patients without an intervention had significantly higher odds of major amputation or inpatient death compared to patients who had MinAMP (1.59 times), EVAS (2.08 times), or SVAS (2.12 times). Patients having a minor amputation had higher odds of major amputation or inpatient death compared to EVAS (1.31 times) and SVAS (1.33 times). The estimated incremental expenditures PMPM for patients with a major amputation was $5,165. CONCLUSIONS: This study of a national payer database found that revascularization reduces the risk of a major amputation or inpatient death for patients with CLI. Also, expenditures are higher when a major amputation occurs, costing the payer approximately $5,000 per member per month.