Objective:To investigate the effect of remote ischemic conditioning (RIC) on cerebral perfusion and functional outcome in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the Department of Neurology, the Second Affiliated Hospital of Xuzhou Medical University from November 2023 to July 2024 were included prospectively. They were randomly divided into RIC group and control group within 48 hours of onset. The control group received treatment according to the current treatment guidelines, while the RIC group received RIC based on this. At admission, three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) perfusion imaging technology was used to measure the cerebral blood flow and calculate low perfusion regions volume with corrected cerebral blood flow (cCBF) <20 and <30 ml/(100 g·min), respectively; and then 3D-pCASL perfusion imaging was performed again on the 10 th day of admission. The main outcome measure was the functional outcome evaluated using the modified Rankin Scale at 90 days after onset. 0-1 were defined as excellent outcome, 0-2 were defined as good outcome, and >2 was defined as poor outcome. Secondary outcome measures included the National Institutes of Health Stroke Scale (NIHSS) score at 14 days after onset and their changes from baseline, cerebral perfusion parameters and their changes, early neurological deterioration (END), hemorrhagic transformation (HT), and adverse reactions of RIC. Results:A total of 48 patients completed the test and follow-up, of which 32 patients (66.7%) were male, aged 67.60±7.37 years. The median baseline NIHSS score was 3 (interquartile range, 2-5). Etiological classification: 15 patients (31.3%) were large artery atherosclerosis, 28 (58.3%) were small vessel occlusion and 5 (10.4%) were other causes. Thirty-one patients (64.6%) were anterior circulation stroke. Among the 48 patients, there were 28 in the RIC group and 20 in the control group. The time from onset to RIC in the RIC group was 21.89±16.17 hours. There was no significant difference in demographic and baseline data between the RIC group and the control group (all P>0.05). The proportion of patients with excellent outcome (78.6% vs. 50.0%; P=0.038) and good outcome (89.3% vs. 60.0%; P=0.042) in the RIC group at 90 days were significantly higher than those in the control group. The NIHSS score and changes at 14 days were also significantly better than those in the control group (all P<0.05). In addition, the volume of low perfusion region with cCBF <20 and <30 ml/ (100 g·min) in the RIC group after treatment decreased compared to the baseline, while the control group slightly enlarged, and the difference between the two groups was statistically significant ( P<0.05). There was no significant difference in the incidence of END and HT between the RIC group and the control group (all P>0.05). Multivariate logistic regression analysis showed that RIC was an independent protective factor for good outcome (odds ratio 9.182, 95% confidence interval 1.579-53.401; P=0.014) and excellent outcome (odds ratio 9.982, 95% confidence interval 1.257-79.230; P=0.030) at 90 days. There were no serious adverse reactions observed in the RIC group. Conclusion:RIC can reduce the volume of low perfusion region in patients with AIS, improve neurological function and clinical outcome, and has no serious adverse reactions.