A positive fluid balance may evolve to fluid overload and associate with organ dysfunctions, weaning difficulties, and increased mortality in ICU patients. We explored whether individualized fluid management, assessing fluid responsiveness via a passive leg-raising maneuver (PLR) before a spontaneous breathing trial (SBT), is associated with less extubation failure in ventilated patients with a high fluid balance admitted to the ICU after liver transplantation (LT). We recruited 15 LT patients in 2023. Their postoperative fluid balance was +4476 {3697, 5722} mL. PLR maneuvers were conducted upon ICU admission (T1) and pre SBT (T2). Cardiac index (CI) changes were recorded before and after each SBT (T3). Seven patients were fluid-responsive at T1, and twelve were responsive at T2. No significant differences occurred in hemodynamic, respiratory, and perfusion parameters between the fluid-responsive and fluid-unresponsive patients at any time. Fluid-responsive patients at T1 and T2 increased their CI during SBT from 3.1 {2.8, 3.7} to 3.7 {3.4, 4.1} mL/min/m2 (p = 0.045). All fluid-responsive patients at T2 were extubated after the SBTs and consolidated extubation. Two out of three of the fluid-unresponsive patients experienced weaning difficulties. We concluded that fluid-responsive patients post LT may start weaning earlier and achieve successful extubation despite a high postoperative fluid balance. This highlights the profound impact of personalized assessments of cardiovascular state on critical surgical patients.