Background: Modified radical mastectomy (MRM) remains the most commonly performed operative procedure for breast cancer today. Conventional MRM using electrocautery or scalpel is associated with a moderate degree of operative morbidity. Ultrasonic dissection using the harmonic scalpel has recently emerged as a safe alternative to electrocautery. Aim: To test the hypothesis that the use of a harmonic scalpel results in less estimated blood loss, postoperative pain, drainage volume, and duration of surgery, as well as fewer complications, such as flap necrosis, seroma, and surgical site infection, than conventional electrocautery without prolonging the operative time. Methods: A prospective randomized single blinded controlled study in which the operative and postoperative details of twenty breast cancer patients who underwent modified radical mastectomy for pathologically proven breast cancer using the harmonic scalpel (group A) were compared with twenty matched controls operated with electrocautery (group B) in Ain shams university hospitals between April 2014 and march 2016. Results: There was no significant difference in the operating time between the harmonic scalpel and electrocautery group (108 and 112.5 mins, p 0.924). The blood loss (100-170 ml) as compared to electrocautery group (250-350 ml) and drainage volume (300-450 ml) in group A versus (600-800 ml) in group B; were significantly lower (p<0.001) in the harmonic scalpel group. Also, statistically significant lower postoperative pain in the harmonic group was documented. There was a significant reduction of drain days in harmonic scalpel group (average 4 vs 8.5 days). There was no significant difference in the wound complications rate between two groups. Conclusion: Modified radical mastectomy using harmonic scalpel is feasible and significantly reduces the blood loss and duration of drainage as compared to electrocautery.