Administration of vasopressors or inotropes during liver transplant surgery is almost universal, as this procedure is often accompanied by massive haemorrhage, acid–base imbalance, and cardiovascular instability. However, the actual agents that should be used and the choice between a vasopressor and an inotrope strategy are not clear from existing published evidence. In this prospective, randomised, controlled and single-blinded study, we compared the effects of a vasopressor strategy on intra-operative blood loss and acid–base status with those of an inotrope strategy during living donor liver transplantation. Seventy-six adult liver recipients with decompensated cirrhosis were randomly assigned to receive a continuous infusion of either phenylephrine at a dose of 0.3–0.4 μg.kg−1.min−1 or dopamine and/or dobutamine at 2–8 μg.kg−1.min−1 during surgery. Vascular resistance was higher over time in the phenylephrine group than in the dopamine/dobutamine group. Estimated blood loss was significantly lower in the phenylephrine group than in the dopamine/dobutamine group (mean (SD) 4.5 (1.8) l vs 6.1 (3.4) l, respectively, p = 0.011). Patients in the phenylephrine group had lower lactate levels in the late pre-anhepatic and the early anhepatic phase and needed less bicarbonate administration than those in the dopamine/dobutamine group (median (IQR [range]) 40 (0–100 [0–160]) mEq vs 70 (40–163 [0–260]) mEq, respectively, p = 0.018). Postoperative clinical outcomes and laboratory-measured hepatic and renal function did not differ between the groups. Increased vascular resistance and reduction of portal blood flow by intra-operative phenylephrine infusion is assumed to decrease the amount of intra-operative bleeding and thereby ameliorate the progression of lactic acidosis during liver transplant surgery.