Background. Exhaustive hemostasis is essential to successful thyroidectomy. Electrocoagulation to control bleeding has the potential risk of injuring the surrounding structures from lateral dispersion of heal. The Harmonic Scalpel (HS) cuts and coagulates simultaneously using mechanical vibration rather than high temperatures. Because its use in thyroidectomies has been limited, we sought to compare procedure parameters and complications of thyroidectomies performed using the HS with those using electrocoagulation. Methods. Sixty patients were randomized into 2 surgical groups, HS and the standard technique using electrocautery and ligatures as the primary hemostatic method. A sample t test or Wilcoxon rank sum test was used to compare the following parameters: operative time, number of ligatures, blood loss, pain intensity, need for extra dose(s) of analgesic, incidence of recurrent laryngeal nerve palsy, and hypoparathyroidism. Results. Both groups of 30 patients were comparable in age, gender, and nature of disease. In 38 patients (63%), surgery was performed for benign disease, and in 22 (37%), for differentiated carcinoma. Operative time (arithmetic mean +/- SD) was 25 minutes less in the HS group (96 +/- 23 vs 121 +/- 34, P = .005). Median number of ligatures in the HS group was 1 (range, 0-7) versus 17 (range, 6-28) (P < . 001). Mean blood loss, estimated by gauze weight, was less with HS (35 +/- 27mL vs 54 +/- 51 mL, P = .06). Drainage during the first 24 postoperative hours and pain intensity during the first postoperative week were similar in both groups. There were no episodes of persistent nerve palsy or hypoparathyroidism in either group. Conclusion. The use of HS in thyroidectomies requires less of operative time than does electrocoagulation.