To determine plasma fetuin-A levels in hypothyroid patients before and after treatment with l-thyroxine (T4) and to determine the relation between plasma fetuin-A levels with cardiovascular risk factors. A prospective, controlled, single-blind study. Forty-four treatment-naive female patients diagnosed with hypothyroidism and 39 age- and sex-matched control subjects were enrolled. Anthropometric measurements, blood pressure, plasma TSH, fetuin-A, free T4, LDL-cholesterol, triglyceride, C-reactive protein, fibrinogen levels, and brachial artery flow-mediated dilatation were measured. All measurements were repeated after 3 months in the control group and 3 months after the attainment of euthyroidism with l-T4 replacement in the hypothyroid group. Baseline data were compared between the two groups. Posttreatment plasma fetuin-A levels of hypothyroid patients were compared with baseline levels of both groups. The relationship between plasma fetuin-A, TSH levels, and other cardiovascular risk factors was evaluated. Plasma fetuin-A levels were ∼20% lower in hypothyroid female patients compared with the controls (P=0.0001). Fetuin-A levels increased by ∼20% in hypothyroid patients after achievement of euthyroidism (P=0.0001) and were no longer different compared with controls (P=0.38). There was a negative correlation between plasma TSH and fetuin-A levels (r=-0.79; P=0.001). There was no significant correlation between plasma fetuin-A levels and cardiovascular risk factors within or between groups. The fetuin-A levels were normalized with thyroid hormone treatment. Plasma fetuin-A levels are reduced in female patients with hypothyroidism, which are restored to normal during restoration of euthyroidism. There was no relation with cardiovascular risk factors.