Context: Although some endocrine surgeons administer Lugol solution to decrease thyroid gland vascularity, there is still not an agreement on its effectiveness. Objective: The aims of this clinical trial are to evaluate thyroid blood flow and microvessel density in patients with Graves’ disease who received Lugol solution treatment preoperatively. Design: This was a prospective clinical trial. Setting: This clinical trial took place at a tertiary referral center. Method: Thirty-six patients were randomly assigned to receive either preoperative treatment with Lugol solution (group 1, n = 17) or no preoperative treatment with Lugol solution (group 2, n = 19). Main Outcome Measures: Blood flow through the thyroid arteries of patients with Graves’ disease was measured by color flow Doppler ultrasonography. The microvessel density (MVD) was assessed by immunohistochemical and Western blot analysis of the level of expression of CD-34 in thyroid tissue. The weight and blood loss of the thyroid gland were measured in all patients. Results: The mean blood flow, MVD, CD-34 expression, and blood loss in group 1 patients were significantly lower than those in group 2 patients. There was a negative correlation between Lugol solution treatment and blood flow (r_s = −0.629; P = 0.0001), blood loss (r_s = −0.621; P = 0.0001), MVD (r_s = −0.865; P = 0.0001), and CD-34 expression (r_s = −0.865; P = 0.0001). According to logistic regression analysis, Lugol solution treatment resulted in a 9.33-fold decreased rate of intraoperative blood loss. Conclusion: Preoperative Lugol solution treatment decreased the rate of blood flow, thyroid vascularity, and intraoperative blood loss during thyroidectomy.