Fluid therapy during major hepatic resection aims at minimizing fluids during the dissection phase to reduce central venous pressure, retrograde liver blood flow, and venous bleeding. This strategy, however, may lead to hyperlactatemia. The Acumen assisted fluid management system uses novel decision support software, the algorithm of which helps clinicians optimize fluid therapy. The study tested the hypothesis that using this decision support system could decrease arterial lactate at the end of major hepatic resection when compared to a more restrictive fluid strategy. This two-arm, prospective, randomized controlled, assessor- and patient-blinded superiority study included consecutive patients undergoing major liver surgery equipped with an arterial catheter linked to an uncalibrated stroke volume monitor. In the decision support group, fluid therapy was guided throughout the entire procedure using the assisted fluid management software. In the restrictive fluid group, clinicians were recommended to restrict fluid infusion to 1 to 2 ml · kg-1 · h-1 until the completion of hepatectomy. They then administered fluids based on advanced hemodynamic variables. Noradrenaline was titrated in all patients to maintain a mean arterial pressure greater than 65 mmHg. The primary outcome was arterial lactate level upon completion of surgery (i.e., skin closure). A total of 90 patients were enrolled over a 7-month period. The primary outcome was lower in the decision support group than in the restrictive group (median [quartile 1 to quartile 3], 2.5 [1.9 to 3.7] mmol · l-1vs. 4.6 [3.1 to 5.4] mmol · l-1; median difference, -2.1; 95% CI, -2.7 to -1.2; P < 0.001). Among secondary exploratory outcomes, there was no difference in blood loss (median [quartile 1 to quartile 3], 450 [300 to 600] ml vs. 500 [300 to 800] ml; P = 0.727), although central venous pressure was higher in the decision support group (mean ± SD of 7.7 ± 2.0 mmHg vs. 6.6 ± 1.1 mmHg; P < 0.002). Patients managed using a clinical decision support system to guide fluid administration during major hepatic resection had a lower arterial lactate concentration at the end of surgery when compared to a more restrictive fluid strategy. Future trials are necessary to make conclusive recommendations that will change clinical practice.