Optimal choice of diuretics in perioperative management remains unclear in enhanced recovery after liver surgery. This study investigated the efficacy and safety of tolvaptan (oral vasopressin V2-receptor antagonist) in postoperative management of patients with liver injury and hepatocellular carcinoma. The patients clinically diagnosed with liver cirrhosis were included in this study. Clinical outcomes of 51 prospective cohort managed with a modified postoperative protocol using tolvaptan (validation group) were compared with 83 patients treated with a conventional management protocol (control group). Postoperative urine output were significantly larger and excessive body weight increase were reduced with no impairment in renal function or serum sodium levels in the validation group. Although the total amount of discharge and trend of serum albumin level were not significantly different among the groups, global incidence of postoperative morbidity was less frequent (19.6% vs. 44.6%, P=0.005) and postoperative stay was significantly shorter (8 days vs.10 days, P=0.008) in the validation group compared with the control group. Tolvaptan could be safely used for the patients with injured liver in postoperative management after hepatectomy and potentially advantageous in the era of enhanced recovery after surgery with its strong diuretic effect and better fluid management.