Abstract： Objective： To observe the clinical effect of modified Xingshen Huoxue Tongluo Decoction combined with butylphthalide sequential therapy for acute ischemic stroke (AIS). Methods：A total of 92 AIS patients were divided into the observation group and the control group according to the random number table method， with 46 patients in each group. Both groups received routine basic treatment， and the control group was treated with butylphthalide sequential therapy. The observation group was treated with modified Xingshen Huoxue Tongluo Decoction combined with butylphthalide sequential therapy. Both groups were treated for four weeks. Compared the traditional Chinese medicine (TCM) syndrome scores， National Institutes of Health Stroke Scale (NIHSS) scores， Mini-Mental State Examination (MMSE)， and Fugl-Meyer Assessment Scale (FMA) scores between the two groups before and after treatment. Compared cerebral blood flow (CBF)，cerebral blood volume (CBV)，time to peak (TTP)，mean transit time (MTT)， and the levels of endothelin-1 (ET-1) and nitric oxide (NO) before and after treatment in the two groups. Evaluated the clinical effects and incidence of adverse reactions in the two groups. Results：During the treatment period， one case was excluded from the observation group and 45 cases were included in the study；two cases were excluded from the control group and 44 cases were included in the study. After treatment， the total effective rate was 95.56% in the observation group， which was higher than that of 79.55% in the control group (P＜0.05). After treatment，the TCM syndrome scores，NIHSS scores，TTP， MTT， and serum ET-1 levels in both groups were declined when compared with those before treatment (P＜0.05)，and MMSE scores，FMA scores，CBF，CBV，and serum NO levels were increased (P＜0.05)； the TCM syndrome score，NIHSS score，TTP，MTT，and serum ET-1 level in the observation group were lower than those in the control group (P＜0.05)， and the MMSE score， FMA score， CBF， CBV， and serum NO level were higher than those in the control group (P＜0.05). The incidence of adverse reactions was 8.89% in the observation group and 11.36% in the control group， with no significant difference (P＞ 0.05). Conclusion： The combination of Xingshen Huoxue Tongluo Decoction and butylphthalide sequential therapy has a significant therapeutic effect on AIS， which can repair patients' neurological function， improve cognitive and motor function，improve cerebral blood flow perfusion and endothelial function，and has high safety.