Objective To compare the disadvantages and advantages of open thyroid surgery when using the harmonic scalpel (HS) vs conventional hemostasis (CH). Methods One hundred and fifty-one patients and 70 patients underwent thyroid surgery with HS or CH respectively. The tumor diameter, incisional length, the total operative time, thyroidectomy time, intraoperative bleeding volume, postoperative drainage volume and surgical complications were compared. The incisional length and the surgical complications in and after learning curve with harmonic scalpel were compared. Results There was no significant difference between the HS and CH group at baseline. Incisional length, total operative time, thyroidectomy time, intraoperative bleeding volume and postoperative drainage volume in HS group were significantly lower than those of CH group (P＜0.001); the surgical complications showed no significant difference between the HS and CH group (Pgt;0.05); the incisional length after learning curve was shorter than that in learning curve in HS group (P＜0.05); the surgical complications after learning curve were significantly lower than that in learning curve in HS group (P＜0.001). Conclusion HS provides significant advantages over conventional hemostasis in open thyroid surgery. However, it can’t be used in a blindly exclusive way but be combined with conventional knot tying appropriately.