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Objective The aim was to compare between Focus harmonic scalpel and conventional hemostasis in open total thyroidectomy regarding operative time, postoperative complications (hypocalcemia and recurrent laryngeal nerve injury), postoperative blood drainage volume, postoperative pain, and hospital stays. Background Thyroidectomy is one of the most common operations, and many studies have been done to improve the technique of thyroidectomy. Therefore, the author conducted this study to determine if Focus harmonic scalpel is effective in thyroidectomy or not. Materials and methods This study is a prospective, comparative, randomized, and descriptive study of 40 patients having nontoxic multinodular goiter. The patients were divided into two groups: group A was subjected to open total thyroidectomy with Focus harmonic scalpel (20 patients), and group B was subjected to open total thyroidectomy with conventional hemostasis (20 patients). Both groups were compared for age, sex, operative time, postoperative complications (hypocalcemia and recurrent laryngeal nerve injury), postoperative blood drainage volume, postoperative pain, and hospital stays. Results Use of Focus harmonic scalpel in open total thyroidectomy leads to shorter operative time, asP value was highly significant; decrease of postoperative blood drainage volume, asP value was significant; decrease of postoperative pain, asP value was highly significant; and shorter postoperative hospital stays, asP value was significant; however, it does not decrease the rate of postoperative complications (hypocalcemia and the Recurrent laryngeal nerve (RLN) injury), asP value was nonsignificant. Conclusion In open total thyroidectomy, the Focus harmonic scalpel is a reliable and safe tool. Its use is more effective than conventional hemostasis. The surgical operative time and the hospital stay are shorter. The postoperative blood drainage volume is reduced; furthermore, the postoperative pain is less. However, the rates of transient hypocalcemia and recurrent laryngeal nerve injury are statistically nonsignificant.