Introduction: To study the effects of levothyroxine (LT4) administration on several diagnostic indices in patients with subclinical hypothyroidism. Materials and Methods: Twenty-seven patients (19 female and 8 male), mean age: 38±13.5 years (range: 17-61) with basal serum TSH levels of 5.0-16.3 mU/L (mean: 8.4±5.2) and normal FT4I were enrolled. Patients were matched and randomly allocated into two treatment groups, LT4 and placebo. In the LT4 group, dosage was titrated to achieve a serum TSH level between 0.3-3.5 mU/L (mean dose, 75±3.8 µg/day). Main outcome measures were: clinical scores, psychomotor tests and serum concentration of thyroid antibodies, lipids, apolipoproteins A and B, paraoxonase, prolactin, sex hormone binding globulin, CPK, calcium, phosphorus, alkaline phosphatase and sodium before and after treatment. Patients had follow-up visits for 11-14 months (mean: 12±0.6). Results: Ten patients in the LT4 group and 13 in the placebo group completed the study. Mean TSH levels changed from 9.5±6.1 to 1.3±1.2 mU/L (p<0.002) and 7.5±3.1 to 18±15.8 mU/L (p<0.002) in the LT4 and placebo groups, respectively. Eleven patients in LT4 group and 9 in the placebo group had goiter at the beginning of study. At final follow-up visit, goiter size increased in 3 patients in the placebo group and decreased in 4 patients in the LT4 group (p<0.05). Mean total cholesterol, LDL-cholesterol, lipoprotein (a) (p<0.045) and SHBG (p<0.001) increased significantly in the placebo group, but did not change in the LT4 group. Clinical hypothyroidism developed in one patient in the placebo group. Other parameters including clinical scores and psychomotor tests were unchanged in both groups. Conclusion: One year after follow-up, significant increase in serum lipids and TSH levels and goiter size were observed in the placebo group. This warrants further attention to patients with subclinical hypothyroidism.