BACKGROUND AND PURPOSE: We conducted a pilot feasibility and safety study of selective brain cooling with intra-arterial infusion of cold saline combined with endovascular reperfusion for acute ischemic stroke. METHODS: Patients with large-vessel occlusion within 8 hours after symptom onset were enrolled. All patients received intra-arterial recanalization combined with infusion of cold isotonic saline (4°C) in the ischemic territory through the angiographic catheter. RESULTS: Twenty-six patients underwent the procedure, which was technically successful in all. The temperature of ischemic cerebral tissue was decreased by at least 2°C during infusion of the cold solution, and systemic temperature was mildly reduced (maximum 0.3°C). No obvious complications related to intra-arterial hypothermia were observed. CONCLUSIONS: Selective brain cooling by intra-arterial infusion of cold saline combined with endovascular recanalization therapy in acute ischemic stroke seems feasible and safe.