Background: Many techniques have been used for liver parenchymal transection. It remains unknown which technique is superior with regards to perioperative outcomes. Vascular staplers have been used to perform liver parenchymal transection; however, evidence of their performance is still lacking. Methods: This is a single center, retrospective, comparative analysis of surgical outcomes of utilizing the stapler technique versus the harmonic scalpel for parenchymal transection during major hepatectomy. Results: Between 2011 and 2016, 176 patients with an otherwise healthy liver underwent right hepatectomy. A vascular stapler was used for parenchymal transection in 82 patients and the harmonic scalpel in 94 patients (control group). Morbidity, relaparotomy rate, and mortality were similar between groups. Median parenchymal transection time was shorter for patients undergoing stapled hepatectomy (7 vs 39 minutes, p<0.001). Median total operative time was also shorter (205 vs 255 minutes, p<0.001). Conclusion: Stapled parenchymal transection during major hepatectomy is feasible and safe. Transection and total operative times are significantly shorter when the stapler technique is employed. Morbidity and mortality rate are comparable between the two group. The stapler technique should be considered a standard method for liver parenchymal transection.