Background: Isotretinoin is a systemic retinoid used to treat acne and it binds receptors which are the member of steroid-thyroid hormone superfamily. Certain types of retinoids may cause abnormalities in serum thyroid function tests (sTFTs) by suppressing thyroid stimulating hormone (TSH). However, it is uncertain whether systemic isotretinoin has any effect on sTFTs.Objective: The aim of the study was to find out if there is any alteration in sTFTs of patients with acne vulgaris treated with systemic isotretinoin. Methods: A total of 51 patients (male/female: 22/29) with severe acne vulgaris treated with a total dose of 120mg/kg isotretinoin were included into the study prospectively. Serum free T3 (fT3), free T4 (fT4) and TSH levels were measured at baseline, 3rd and 6th months of treatment. Results: Mean serum TSH levels at baseline, 3rd and 6th months of treatment were 1.57 +/- 0.67, 2.07 +/- 0.88 and 2.25 +/- 0.86uIU/mL, respectively. Mean serum TSH levels increased significantly following isotretinoin therapy (p < 0.01, p = 0.007 and p < 0.01, respectively). Mean serum fT3 levels at baseline, 3rd and 6th months of treatment were 3.59 +/- 0.57, 3.19 +/- 0.45 and 3.09 +/- 0.61pmol/L, respectively. Mean serum fT4 levels at baseline, 3rd and 6th months of treatment were 1.21 +/- 0.19, 1.09 +/- 0.16 and 1.11 +/- 0.19pmol/L, respectively. Mean serum fT3 and fT4 levels decreased significantly at 3rd and 6th months compared to baseline levels (p < 0.01 and p < 0.01, p < 0.01 and p = 0.001, respectively). Conclusion: Systemic isotretinoin therapy causes significant alterations in sTFTs. Dose dependent or long-term effects of systemic isotretinoin on sTFTs needs further evaluation.