Abstract Background The ultrasonic scalpel is a recently introduced device in head and neck surgery. Total thyroidectomy is the most common endocrine procedure performed by surgeons. Methods This was an open, phase IV, multicenter, randomized controlled trial (RCT) that compared the use of an ultrasonic scalpel with a conventional technique in patients who underwent total thyroidectomy. The outcomes were surgical complication rate, operative time, drainage volume, postoperative pain, and costs. Results In all, 261 patients were included in 11 centers. There was a mean difference of 17% of operative time in favor of the ultrasonic scalpel group. There were no differences in postoperative complications. There was a difference in costs of 14% in favor of the ultrasonic scalpel group, but it was not statistically significant. Conclusions The use of an ultrasonic scalpel was as safe as that of the conventional technique and had the advantage of a shorter operative time and lower postoperative drainage. Costs were not different between groups. © 2012 Wiley Periodicals, Inc. Head Neck, 2012