Revascularization of acutely ischemic lower limbs is associated with high mortality and high rates of rethrombosis, limb loss, massive edema, and compartment syndrome. These complications may be due to revascularization syndrome. The effects of hypertonic mannitol used during revascularization of acutely ischemic lower extremities were studied. In an isolated canine hind limb model, revascularization of the limb via a Dacron graft after 90 minutes of ischemia resulted in tissue edema and decreased flow. The low flow state (50% of control) for two hours after reperfusion was associated with thrombosis at the anastomosis. Use of hypertonic mannitol reversed the reperfusion syndrome and prevented graft thrombosis. Therefore, 15 consecutive patients with acute lower extremity ischemia and threatened limb loss were treated with hypertonic mannitol during emergency thromboembolectomy. Fourteen patients survived and had excellent results without any rethrombosis. Compartment syndrome was absent. Results of this clinical trial suggests that hypertonic mannitol may be useful in the management of acute arterial ischemia.