Objective To investigate the clinical efficacy and safety of guhong injection in the treatment of patients with acute ischemic stroke.Methods A multicenter prospective study was conducted with a randomized， double-blind， parallel-controlled clinical trial design. A total of 2 000 patients with acute ischemic stroke who attended 31 hospitals from July 22， 2021 to April 30， 2024 were enrolled， and after screening and randomization， 999 patients were enrolled in the experimental group and 1 000 were enrolled in the control group. The patients in the experimental group were given Guhong injection， while those in the control group were given placebo （normal saline）， and the course of treatment was 10 days for both groups. The two groups were compared in terms of the change in modified Rankin Scale （mRS） score on day 90 after disease onset， as well as the proportion of subjects with an mRS score of ≤2 after treatment， and the adverse reactions during treatment were observed and recorded for both groups.Results On day 90 after disease onset， the experimental group had a significantly higher proportion of patients with an mRS score of ≤2 than the control group ［71.10% （710/999） vs 65.10% （651/1 000）， P<0.05］. There was no significant difference in the incidence rate of adverse reactions between the experimental group and the control group during treatment （0.70% vs 0.40%， P>0.05）. The experimental group showed comparable safety to the control group based on a comprehensive safety assessment of adverse reactions， clinical laboratory tests， electrocardiographic findings， and vital signs.Conclusions Guhong injection has the advantages of marked clinical efficacy and good safety and reliability and can effectively improve clinical compliance and the clinical symptoms and quality of life of patients with acute ischemic stroke， and therefore， it holds promise for clinical application. ［Journal of International Neurology and Neurosurgery, 2024, 51(4): 1-7］