Objective To determine the relationship between lesion locations and quality of life (QOL) in patients with ischemic stroke. Methods The QOL of 456 stroke survivors was assessed two years after the occurrence of stroke. The EQ-5D was used for measuring QOL. Lesion locations of the patients were identified with CT, MRI and clinical features. Risk factors associated with QOL were identified using a multi-level model. Results Among the 456 stroke survivors, 61.62% (3/5) had ACI lesions, and more than half of ACI occurred in the subcortex. The number of stroke survivors with left and right hemisphere lesions was almost equal. Different QOL was found between stroke survivors with a right-side brain lesion and those with non-brain lesions ( P<0.001). Significant differences in QOL were also found between those with a subcortex of anterior circulation lesion and others ( P<0.044). Conclusion Lesion locations are associated with QOL. Future studies should pay attention to lesion locations classified by vascular territory and brain anatomical structures and size of lesions.