OBJECTIVE: The ultrasonic scalpel is a surgical shear that uses high-frequency mechanical energy to enable simultaneous vessel sealing and tissue coagulation at the same time. We conducted a prospective randomized study to compare the outcome of total thyroidectomy using the ultrasonic scalpel versus standard clamp and tie (CT) procedure in terms of safety, operative time, overall drainage volume, complications, hospital stay. METHODS: Between January 2008 and December 2010, 200 patients (130 women, 70 men; mean age 46 years) undergoing thyroidectomy were randomized into two groups: group A, where CT technique were used, and group B, where the ultrasonic device was used. RESULTS: There was no significant differences between the two groups in terms of age, gender, indication for thyroidectomy, thyroid gland weight and diameter, histopathologic diagnosis, preoperative and postoperative serum calcium levels, postoperative complications and reoperative thyroid surgery. In group B there is a statistically significant reduction of the operative times (63 ± 9’ vs 85 ± 15’, P<0.001) and overall drainage volume (50 ± 20cc vs 70 ± 25cc, P<0.001). CONCLUSIONS: The ultrasonic scalpel is safe, effective, useful, and time-saving alternative to the traditional suture ligation technique for thyroid surgery. They simplified total thyroidectomy, eliminating the need for clamp-and-tie maneuvers while achieving efficient hemostasis. Our study shows that the use of ultrasound in thyroid surgery reduces significantly surgical time and overall drainage volume. Furthermore, we also verified a decrease in hospitalization time, postoperative pain and blood loss, without increasing complication rates, for patients who underwent total thyroidectomy with the ultrasonically activated shear.