Transaxillary endoscopic dual-plane breast augmentation is becoming increasingly mature. The intraoperative separation of the implant into the space is often performed using monopolar cautery. The use of the harmonic scalpel has proved more beneficial in several surgeries. However, no study has ever addressed the effects of harmonic scalpel usage compared to monopolar cautery in transaxillary endoscopic dual-plane breast augmentation. In this randomized controlled study, we enrolled patients (n = 78) who underwent breast augmentation in our hospital from January to October 2022. Participants were randomized with an intentional unequal allocation ratio (2:1 in the harmonic scalpel group: monopolar cautery group). Outcome measures included: total postoperative drainage volume, postoperative drainage volume for the first 24 h, number of postoperative drainage days, daily pain scored through the visual analog scale, operative time, and reoperation rate. A total of 51 patients in the harmonic scalpel group and 24 patients in the monopolar cautery group were analyzed. Overall, in comparison to the monopolar cautery group, the harmonic scalpel group showed improved total postoperative drainage volume, postoperative drainage volume for the first 24 h, number of postoperative drainage days, and postoperative pain scores. No differences were found regarding operative time and reoperation rate. Compared with monopolar cautery, harmonic scalpel usage in transaxillary endoscopic breast augmentation has evident advantages regarding postoperative drainage and patients' pain scores, making it an instrument worth of recommendation.