The present study aimed to compare the effect of two different preparations of L-thyroxine in serum TSH and serum Free T4 levels in patients with primary hypothyroidism due to a previous total thyroidectomy for differentiated thyroid cancer and multinodular goiter with compression symptoms to cervical structures. Seventy-two patients were recruited but three had elevated serum Tg after withdrawal of L-T4, six did not completed the protocol and two had partial thyroidectomy. The 61 patients finally included were, randomly, assigned to two groups: Group I (n=31) was treated with a daily single dose of 100µg of Levoid® and Group II (n=30) patients similarly were instructed to take 100µg of Puran T4®. On the Basal phase (after L-T4 withdrawal for 3-4 weeks) serum TSH values were 46.26 ± 26.18µU/mL (Group I) and 41.9 ± 23.1µU/mL for Group II (mean ± SD, p=NS). Concentrations of serum TSH decreased significantly with time (at 15, 30 and 45 days) and serum free T4 rose significantly during L-T4 treatment. There was no statistical difference between groups in each time period. We concluded that both preparations of L-T4 are equally effective for treatment of primary hypothyroidism without any reportable side effects at the dose of L-T4 that was used.