Background and purpose: The neuroprotection of hypothermia in acute ischemic stroke has been proved by many animal experiments. However, the whole body cooling needs relatively longer time to reach target temperature and has many adverse effects. In this trial, we focused on the feasibility and safety of selective brain cooling by intra-arterial infusion of cold saline in patients with acute ischemic stroke during endovascular revascularization procedure. Methods: Patients who suffered from large proximal vessel occlusions within 8 hours after symptoms onset were enrolled. All patients received intra-arterial recanalization combined with infusion of isotonic saline (4°C) into ischemic territory through angiographic catheter. Vital signs, physiological parameters, adverse effects and complications were analyzed to evaluate feasibility and safety. Modified Rankin Scale (mRS) and mortality at 3 months were analyzed to evaluate clinical outcome. Results: 26 patients with a mean age of 58.4±9.56 years and median NIHSS score of 18 (14-20) were enrolled. The median time from symptoms onset to groin puncture was 383 (195-432) minutes. physiologic parameters were relatively stable before, during, and after revascularization procedures. The temperature of ischemic cerebral tissue was dropped at least 2°C theoretically during infusion of the cold solution, and rectal temperature was mildly dropped (maximum 0.3°C), but soon returned to normal after infusion. Complications in these patients included pneumonia (n=10), mild vascular spasm (n=4), melena (n=2), deep vein thrombosis (n=1), coagulation disorder (n=2). No intracranial hemorrhage, shivering, groin hematom, acute congestive heart failure, renal inadequacy, platelet count<100 000/nL and arrhythmia were observed. At 3 months, 15 patients had good outcome (mRS, 0-2) and 11 patients with poor outcome (mRS, 3-6). Conclusions: Selective brain cooling by intra-arterial infusion of cold saline combined with endovascular recanalization therapy in acute ischemic stroke is feasible and safe.