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Introduction: Hemodynamic disturbance is a common problem in patients undergoing thyroid surgery. It may be due to episodic increases in thyroid hormones (thyroid storm) or stimulation of the carotid sinus baroreflex. The aim of the present study was to investigate effectiveness of the pre-operative oral Clonidine on reducing these hemodynamic changes during total thyroidectomy surgery., Methods: In a prospective, randomized, double-blind study, 80 patients scheduled for elective total thyroidectomy were randomized to receive either 0.2 mg Clonidine (n=40) or a matched placebo (n=40) orally sixty minutes before entering the operating room. Hemodynamic variables, the duration of surgery, estimated amount of blood loss and the dose of administered remifentanil were recorded for further analysis., Results: Oral Clonidine was found to be significantly better in maintaining stable hemodynamics compared to the control group. Also, In the Clonidine group, the estimated amount of blood loss (110.4±10 ml vs. 182.2±11.4 mL, P =0.04), duration of the surgery (78.26±55.2 min vs. 105.16±61.75 min, P =0.027) and administered dose of remifentanil (26.67±6.6 μg vs. 216.2±14.8 μg, P =0.01) were also significantly lower than the control group., Conclusion: Pre-operative administration of 0.2 mg oral Clonidine in patients undergoing total thyroidectomy results in improved perioperative hemodynamic stability and reduced response to perioperative stress., Competing Interests: Authors declare that there is not any conflict of interests about this study., (© 2023 The Author(s).)