Objective:To investigate the effect of white matter hyperintensities (WMHs) location on the clinical outcomes in patients with anterior circulation acute ischemic stroke (AIS) after intravenous thrombolysis.Methods:Patients with anterior circulation AIS treated with alteplase intravenous thrombolysis in Xuzhou Central Hospital from February 2015 to February 2020 were enrolled retrospectively. The severity of periventricular WMHs (PWMHs) and deep WMHs (DWMHs) was assessed by Fazekas scale. According to the score of the modified Rankin Scale at 90 d after onset, the patients were divided into good outcome group (0-2) and poor outcome group (3-6). The demographic and clinical data were compared between the two groups. Multivariate logistic regression analysis was used to investigate the effect of WMHs location on the clinical outcome in AIS patients treated with intravenous thrombolysis. Results:A total of 408 patients with anterior circulation AIS were enrolled in the study, including 272 males (66.7%) and 136 females (33.3%). Their age was 64.1±12.1 years (range, 40-92years). The baseline median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range, 4-16). Three hundred and fourteen patients (77.0%) were in the good outcome group and 94 (23.0%) were in the poor outcome group. There were significant differences in age, atrial fibrillation, diabetes mellitus, baseline NIHSS score, blood glucose level before thrombolysis, etiological classification of stroke, PWMHs, DWMHs, hemorrhagic transformation, early neurological deterioration and stroke recurrence between the two groups (all P<0.05). Multivariate logistic regression analysis showed that moderate to severe PWMHs were significantly and independently associated with the poor outcomes in patients with anterior circulation AIS treated with intravenous thrombolysis at 90 d after onset (odds ratio 2.357, 95% confidence interval 1.086-5.115; P=0.030). Other independent related factors included age, baseline NIHSS score, etiological classification of stroke (large artery atherosclerosis and cardiogenic embolism), early neurological deterioration, hemorrhagic transformation, and stroke recurrence. Conclusion:Moderate to severe PWMHs is an independent risk factor for poor outcomes at 90 d after onset in patients with anterior circulation AIS treated with intravenous thrombolysis.