One-third of the patients with symptomatic PAD will get worse during the course of their disease and may develop rest pain with or without skin ulcers. This condition is called critical limb ischemia (CLI).

Some experts consider believing CLI is a systemic condition rather than a local malperfusion to a limb. Patients with CLI have a higher chance of major limb amputation, death or any major disability and compares the patient was just PAD. Early intervention with a multidisciplinary approach is the best way to treat CLI.