Objectives <p>Hypothyroidism is a disorder characterized by insufficient thyroid hormone production; its manifestations can lead to impaired function and health-related quality of life. This study is aimed to compare the quality of life (QoL) in levothyroxine(LT4)-treated patients with serum thyroid hormone levels equivalent to those of healthy controls.</p> Materials and methods <p>This cross-sectional investigation enrolled 220 participants, including 110 hypothyroid individuals treated with LT4 as the case group and 110 euthyroid subjects as the controls. Demographic variables (age, sex, marital status, occupation, and education), QoL, and mean thyroid function indices (Thyroid Stimulating Hormone, Triiodothyronine, and Thyroxine) were assessed and compared between the two groups. The QoL was evaluated using the World Health Organization Quality Of Life (WHOQOL) -BREF Questionnaire.</p> Results <p>Our findings demonstrated that QoL scores across the subscales of physical health, mental health, social relationship, environment, and overall QoL and general health were significantly lower in the LT4-treated (case) group compared to the healthy (control) group (<i>p</i> &lt; 0.001). Multiple linear regression showed that disease status (B=-18.61, <i>p</i> &lt; 0.001), education level (B = 4.42, <i>p</i> = 0.005), and mean Triiodothyronine (T3)(B = 0.41, <i>p</i> &lt; 0.001) are independent predictors for QoL.</p> Conclusions <p>Patients on LT4 therapy have a significantly lower QoL despite achieving serum thyroid hormone levels equivalent to those of healthy controls.</p>