Introduction Over the last two decades, many studies have been done to assess the best technique and device for liver resection. On a trial to solve this issue, we conducted this study. Materials and methods Starting from January 2017, 60 patients underwent formal hepatectomies in Ain Shams University Hospitals using two different devices. A total of 30 patients with a mean age of 43 years underwent hepatectomy using cavitron ultrasonic surgical aspirator (CUSA) and the other 30 patients with a mean age of 45.53 years by using the harmonic scalpel. As for the sex, the women were more than men in the harmonic group (n=23 of 30) while in the CUSA group they were less (n=10 of 30). All patients underwent formal hepatectomies; in the CUSA group the majority had right hepatectomy (n=16 of 30) while in the harmonic group the majority had left hepatectomy (n=18 of 30). Results In the CUSA group, the mean operative time was 226.93 min and the resection time was 117.77 min while in the harmonic group, the mean operative time was 202.33 min and the resection time was 102.5 min. In the CUSA group, the mean amount of blood loss was 736.67 ml and the mean blood transfusion was 3.17 units of Packed red Blood Cells (PRBCs), while in the harmonic group, the mean amount of blood loss was 516.67 ml and the mean blood transfusion was 2.57 units of PRBCs. In the CUSA group, 11 patients suffered from postoperative bleeding and seven patients had abdominal hematoma by ultrasound and four patients needed reexploration. In the harmonic group, four patients suffered from postoperative bleeding and one patient had abdominal hematoma by ultrasound and one patient needed reexploration. Conclusion In our study, apart from the biliary complications, we believe that harmonic scalpel is faster and safer than the cusa. Yet another study should be conducted to assess the safety and efficacy of using both devices in combination.