OBJECTIVE: Thyroid hormones play important roles in most organs, including the brain. This study aimed to explore the association between thyroid hormones and the severity of white matter hyperintensities (WMH) in patients without intracranial arterial stenosis, which is a common manifestation in the brain. METHODS: This retrospective study included 304 patients at the Department of Neurology in Nantong First People's Hospital between June 2018 and June 2020. Thyroid hormone levels and other laboratory data were collected on the day after admission. The patients were divided into two WMH burden groups based on Fazekas scores as follows: ''mild-moderate group'' and ''severe group.' ' RESULTS: The severe WMH group had higher ages (P=0.000), higher serum concentration of fibrinogen (P=0.040), higher concentration of creatinine (P=0.040), lower concentration of low-density lipoprotein (P=0.013), and higher concentration of free thyroxine (FT4) (P=0.003). The prevalence of cerebral microbleeds (CMBs) increased with increasing quartiles (P=0.023). Multivariable logistic regression and ordinal regression analysis showed that higher concentrations of FT4, age, and CMBs were also independent risk factors for severe WMH. The concentrations of FT4 were grouped according quartiles. The results showed that the prevalence of severe WMH increased with higher quartiles. This correlation persisted after adjusting for risk factors such as sex, age, history of hypertension, diabetes, drinking history, and smoking history. CONCLUSION: Our results support the hypothesis that FT4 is associated with the severity of WMH in patients without intracranial arterial stenosis. In addition, age and CMBs are independently related to the severity of WMH.