This study evaluated the safety and feasibility of a technique of liver resection named dual-wield parenchymal transection technique (DWT), using cavitron ultrasonic surgical aspirator (CUSA) and water-jet scalpel simultaneously. This multicenter, prospective, open-label, and single-arm phase I trial included patients aged 20 years or older with hepatic tumors indicated for surgical resection and scheduled for open radical resection. This study was conducted at two institutions affiliated with the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). The primary endpoint was the proportion of massive intraoperative blood loss (≥ 1000 mL). The secondary endpoints were the amount of blood loss, operative time, parenchymal transection speed, postoperative complications, and mortality. The safety endpoints were device failure and adverse events associated with devices. From June 2022 to May 2023, 20 patients were enrolled; one was excluded and 19 were included in the full analysis set (FAS). In the FAS, segmentectomy was performed in nine cases, sectionectomy in four cases, and hemihepatectomy in six cases. Radical resection was achieved in all patients. Intraoperative blood loss greater than 1000 mL was observed in five patients (26.3%). The median amount of blood loss was 545 mL (range, 180-4413), and blood transfusions were performed on two patients (10.5%). The median operative time was 346 minutes (range, 238-543) and the median parenchymal transection speed was 1.2 cm2/minute (range, 0.5-5.1). Postoperative complications of Clavien-Dindo classification ≥ Grade 3 occurred in four patients (21.1%). No mortalities occurred in this study. In the safety analysis, there were no device failures or adverse events associated with devices. This study demonstrated the safety and feasibility of DWT for liver resection. The efficacy of the DWT will be evaluated in future clinical trials.