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Harmonic scalpel and LigaSure vessel sealing systems have been suggested as options for saving surgical time and reducing postoperative complications. The aim of the present meta-analysis was to compare surgical time, postoperative complications and other parameters between them in for the open thyroidectomy procedure. Studies were retrieved from MEDLINE, Cochrane Library, EMBASE and ISI Web of Science until December 2015. All the randomized controlled trials (RCTs) comparing Harmonic scalpel and LigaSure during open thyroidectomy were selected. Following data extraction, statistical analyses were performed. Among the 24 studies that were evaluated for eligibility, 7 RCTs with 981 patients were included. The Harmonic scalpel significantly reduced surgical time compared with LigaSure techniques (8.79 min; 95% confidence interval, -15.91 to -1.67; P=0.02). However, no significant difference was observed for the intraoperative blood loss, postoperative blood loss, duration of hospital stay, thyroid weight and serum calcium level postoperatively in either group. The present meta-analysis indicated superiority of Harmonic Scalpel only in terms of surgical time compared with LigaSure hemostasis techniques in open thyroid surgery.