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Background: Subclinical hypothyroidism (SH) is settled whenever high levels of serum thyroid-stimulating hormone (TSH) are detected, whereas free thyroid hormone levels are within the normal range. Benefits and risks of therapy for SH have been debated for 2 decades. However, consensus has not yet been achieved. Besides preventing the progression to overt hypothyroidism, the decision of undertaking replacement therapy in SH is made mainly by basing on the risk of metabolic (dyslypidemia) and subsequent cardiovascular complications., Materials and Methods: A series, made up of 1756 patients (mean age 42,8±16,8, range 0,5-94) and filed from 1984 to 2013, was studied retrospectively. 169 patients were affected by clinical (overt) hypothyroidism (IC: TSH >40). 1587 patients were affected by SH, out of whom 1121 were mild (TSH <10) and 466 medium (TSH ≥ 10 ≤40). The series of patients was properly followed-up. The mean follow-up time was 6 years. In all patients TSH, Ft4, and total cholesterol were evaluated basally and after appropriate (TSH normalized) medical therapy., Results: By medical replacement treatment, clinical hypothyroidism (CI) related hypercholesterolemia decreased significantly in 28%. In SH, the baseline serum cholesterol levels were wide. However, replacement treatment did not reduce such levels. No major cardiovascular accident occurred to any patient over the follow-up period., Conclusions: Hypercholesterolemia is certainly due to CI, therapy reduces cholesterol levels that not always fall below 200 mg/dl and this condition persists over time. SH is not characterized by hypercholesterolemia. Cholesterol levels in these patients are variable equal to the normal people and can not be reduced with thyroxine.