OBJECTIVES: Peripheral arterial disease is associated with significant adverse outcomes, especially in patients with critical limb ischemia (CLI; stages III and IV). At 6 months, the risk of amputation is 35%, and mortality 20%. In patients unsuitable for interventional therapy, treatment with prostanoids may help reduce the risk of adverse outcomes. We aimed to assess the average cost of alprostadil (prostaglandin E1) as treatment for patients with CLI compared with lumbar sympathectomy from the perspective of The Mexican Social Security Institute (IMSS). METHODS: In a clinical trial, alprostadil and lumbar sympathectomy showed similar response rates (Petronella P, et al. Nutr Metab Cardiovasc Dis 2004;14:186–92).Therefore, we conducted a cost minimization analysis based on the direct medical costs of alprostadil (40 µg twice-daily or 60 µg once-daily) administered over 28 days versus lumbar sympathectomy. Relevant costs included acquisition and infusion for alprostadil, and surgical procedure besides hospitalization (9 days) for lumbar sympathectomy. Unit cost for infusion was assumed to be equivalent to an emergency visit at first level of care at IMSS; unit cost of the surgical procedure and standard hospital stay (per day) correspond to the official values for these items at the second level of care at IMSS. UCB Pharma provided the cost for alprostadil. All costs are in 2013 Mexican pesos (MXN; 12.88 MXN = 1 USD, 17.23 MXN = 1 Euro). RESULTS: Costs per patient would be lower with both alprostadil 40 µg twice-daily ($59,640) and alprostadil 60 µg once-daily ($37,884) than with lumbar sympathectomy ($66,084), leading to savings of $6,444 (9.8%) and $28,200 (42.7%), respectively. Alprostadil use remained cost-saving versus lumbar sympathectomy in most of the scenarios evaluated through sensitivity analysis. CONCLUSIONS: These results suggest alprostadil is a cost saving intervention when compared with lumbar sympathectomy for patients with CLI from the Mexican public healthcare perspective.