Objective To investigate the clinical characteristics of the patients with acute ischemic stroke (AIS) caused by large artery atherosclerosis (LAA) or cardioembolism (CE) middle cerebral artery M1 segment occlusion, and to explore the difference of endovascular treatment. Methods The patients with AIS caused by M1 segment occlusion, who received endovascular treatment between Sep. 2014 and Feb. 2018 in our hospital, were recruited and assigned to LAA group and CE group. Clinical characteristics, treatment strategy, postoperative hemorrhage rate and prognosis were analyzed. Results Totally 134 patients were included, and 48 patients were in the LAA group and 86 patients were in the CE group. There were significant differences in the gender and age between the LAA and CE groups (male/female 39/9 vs 40/46, χ²=15.363; average age[62.65±9.76] years vs[69.66±12.43] years, t=-3.371; both P<0.05). Compared with the CE group, the proportion of the patients with hypertension was significantly higher, and the National Institutes of Health stroke scale score on admission was significantly lower in the LAA group (70.8%[34/48] vs 51.2%[44/86], χ²=4.900, P=0.027; 13[7, 16] vs 16[13, 21], Z=-3.603, P<0.001). The proportion of the patients with angioplasty in the LAA group was 52.1% (25/48), which was significantly higher than the proportion in the CE group (4.7%[4/86], χ²=38.121, P<0.01). The incidence of postoperative intracranial hemorrhage was significantly lower in the LAA group than that in the CE gorup (10.4%[5/48] vs 32.6%[28/86], χ²=8.136, P=0.004). There were no significant differences in the incidence of symptomatic intracranial hemorrhage, endovascular recanalization rate, or good prognosis rate or mortality 3 months after operation between the two groups (all P>0.05). Conclusion Compared with the patients with AIS due to LAA M1 segment occlusion, the CE patients have more severe symptoms and higher postoperative hemorrhage rate after endovascular treatment. The strategy of endovascular treatment is different in the two types of AIS, while there are no differences in prognosis and mortality after treatment.