Purpose: Harmonic scalpel (HS) recently turned into an burgeoning tool for dissection and haemostasis in axillary dissection (AD) of breast cancer (BC). Therefore, the authors aimed to evaluate the utility and advantages of HS compared with electrocautery (EC) to perform AD. Materials and Methods: A retrospective case-control study was designed to present the therapeutic effect of HS and EC, respectively. The intraoperative blood loss and operating time, as well as postoperative drainage volume, drainage days, pain, and complications of 23 breast cancer patients who underwent AD using the HS were compared with 23 matched patients who operated with EC by the same surgical team. Results: There was no significant difference in the operating time between the HS and EC groups (p > 0.05). However, the blood loss, axillary total drainage volume, and the chest wall total drainage volume were significantly lower in HS than those in the EC group (p < 0.001). In addition, compared with EC group, a significant reduction of draining days was observed in HS group (p < 0.05). Moreover, pain assessment showed only two stabbing pain in the control group (8.6%) and one burning pain in the case group (4%). Also, no postoperative complications such as wound infections and chest wall seroma formation were found. Conclusions: The usage of HS showed a significant reduction in the blood loss, drainage volume, and duration of drainage compared to electrocautery in AD of BC.