Objective: The significance of dyslipidemia in subclinical hypothyroidism (SH) and the effect of thyroid substitution on lipids remain controversial. The present study aimed to assess the association of SH with lipid abnormalities and to quantify the effect of L-thyroxine therapy on serum lipid profiles. Design: Serum lipid parameters of 66 patients with SH and 75 age-and sex-matched euthyroid controls were evaluated in a cross-sectional study. Results: Patients with SH had higher total cholesterol (TC) ð222^45 (S.D.) vs 190^32 mg=dlÞ; lowdensity lipoprotein cholesterol (LDL-C) ð139^28 vs 118^39 mg=dlÞ; apolipoprotein B ð149^21 vs 139^18 mg=dlÞ and lipoprotein (a) (Lp(a)) (median 12.5 (0.8-101) mg/dl vs 7 (0.8 -44) mg/dl) levels compared with euthyroid controls (P , 0:05 for all comparisons). In a follow-up study including 37 patients with SH, all measurements were repeated after restoration of a euthyroid state with incremental doses of L-thyroxine. No significant changes in serum lipid profiles were observed except for a decrease in high-density lipoprotein cholesterol ð59^15 to 55^14 mg=dl; P , 0:05Þ: However, patients with high pre-treatment TC ($240 mg/dl) showed a significant reduction in both TC ð278^28 vs 257^36 mg=dl; P , 0:05Þ and LDL-C ð192^23 vs 173^28 mg=dl; P , 0:01Þ levels. Similar but more pronounced changes were observed in a subgroup of patients with pre-treatment levels of TSH $10 mU/ml. Thyroid autoimmunity had no effect on either the baseline or the posttreatment lipid profile. Conclusion: Although patients with subclinical hypothyroidism exhibit increased levels of the atherogenic parameters (mainly LDL-C and Lp(a)), thyroid substitution therapy does not seem to significantly improve dyslipidemia in the whole group of patients.