Introduction Hepatectomy is the primary treatment for malignant liver tumours. It is crucial to control bleeding during liver parenchymal transection. Methods to reduce central venous pressure (CVP), such as fluid restriction and the use of vasodilators, are essential for minimising bleeding but can lead to haemodynamic instability. Phosphodiesterase-3 (PDEIII) inhibitors such as milrinone have shown efficacy in managing low CVP and maintaining haemodynamic stability. This study investigates olprinone, another PDEIII inhibitor with a potentially strong vasodilatory effect, for its safety and efficacy in CVP management during hepatectomy. Methods and analysis This single-centre phase I trial at Shizuoka Cancer Center evaluates the intraoperative administration of olprinone for open and laparoscopic hepatectomy. The trial employs a 3+3 cohort study design to determine the maximum tolerated dose (MTD) and identify dose-limiting toxicities. The study also assesses the trends in CVP and cir