The aim of this study is to report on the liver transplantation (LT) activity and posttransplant outcome, over time, of patients with grade 3 acute-on-chronic liver failure (ACLF-3) in a single transplant center performing a large number of LTs for patients with ACLF-3. It aims at showing how pre-LT intensive care unit (ICU) management impacts post-LT outcomes, in particular through monitoring the transplantation for ACLF-3 model (TAM) score. A total of 100 patients who had ACLF-3 at the time of LT between 2007 and 2019 were included retrospectively. The cohort was divided in 2 periods, with 50 patients in each period. There was an increase in the number of patients with ACLF-3 who received an LT during the course of the study period and significantly higher 1-year post-LT survival rates in the second period compared with the first period (86% versus 66%, respectively; P = 0.02). Interestingly, patients during both periods had similar severity profiles and scores apart from a significantly lower number of patients with TAM scores >2 at the time of LT in the second period compared with the first period (1 [2%] versus 11 [22%], respectively; P ≤ 0.01). In addition, patients whose clinical condition improved in the ICU (with a TAM score downstaged between admission and LT) had significantly higher post-LT survival rates than those whose TAM score stayed the same or increased: 88% versus 70%, respectively (P = 0.04). This study shows a learning curve in LT for patients with ACLF-3, with optimized ICU management and patient selection leading to increased numbers of LTs for patients with ACLF-3 and improved post-LT outcomes. It also delineates how the TAM score can be used to identify the optimal transplantability window for patients with ACLF-3.