This study aimed to compare the outcomes of modified radical mastectomy (MRM) with the use of a harmonic scalpel versus electrocautery in patients with breast carcinoma. A prospective, non-randomized comparative study conducted from August 2022 to June 2024 on 40 female patients with stage II breast carcinoma undergoing MRM with electrocautery and harmonic scalpel. Patients with MRM by harmonic scalpel exhibited significantly lower intraoperative blood loss (92.50 ± 9.67 mL) than by electrocautery (172.50 ± 30.76 mL) (p-value <.0001). The average operative time was significantly shorter for the harmonic scalpel (111.00 ± 10.71 minutes) than for the electrocautery (169.50 ± 19.32 minutes) (p-value <.0001). Postoperative pain was lower for the harmonic scalpel (visual analog scale (VAS) score 3.75 ± 0.79) than for the electrocautery (VAS score 6.10 ± 0.85) (p-value <.0001). The incidence of flap necrosis was not substantially different between the categories; seroma formation was significantly lower with the use of a harmonic scalpel (p-value <.0001). Subjects in the group of harmonic scalpels also had shorter hospital stays (8.35 ± 0.93 days) compared with the electrocautery group (12.20 ± 1.06 days) (p-value <.0001).