This is a prospective non-randomized cohort study of 113 consecutive patients to investigate the safety and efficacy of a short-duration intraarterial selective cooling infusion (IA-SCI) targeted into an ischemic territory combined with mechanical thrombectomy (MT) in patients with large vessel occlusion-induced acute ischemic stroke (AIS); 45/113 patients underwent IA-SCI with 350 ml 0.9% saline at 4celcius for 15 min at the discretion of the interventionalist. Key parameters such as vital signs and key laboratory values, symptomatic and any intracranial hemorrhage, coagulation abnormalities, pneumonia, urinary tract infections and mortality were not significantly different between the two groups. Final infarct volume (FIV) was assessed on noncontrast CT performed at three to seven days. After an adjusted regression analysis, the between-group difference in FIV (19.1 ml; 95% confidence interval (CI) 3.2 to 25.2; P = 0.038) significantly favored the IA-SCI group. At 90 days, no differences were found in the proportion of patients who achieved functional independence (mRS 0-2) (51.1% versus. 41.2%, adjusted odd ratio (aOR) 1.9, 95% CI 0.8-2.6, P = 0.192). Combining short-duration IA-SCI with MT was safe. There was a smaller FIV and trend towards clinical benefit that will need to be further evaluated in randomized control trials.