Immune checkpoint inhibitors (ICIs) have shown promise in downstaging hepatocellular carcinoma (HCC) for liver transplantation (LT), enabling previously ineligible patients to meet transplant criteria. However, their use raises concerns about post‐transplant acute rejection (AR) based on data lacking information regarding standardized management pathways and notably perioperative protocols, including immunosuppression protocols and monitoring.

This study evaluated 59 LT recipients divided into three groups (two control groups), including 13 ICI‐exposed patients (third group). All groups followed a standardized immunosuppression protocol and monitoring embedded into an enhanced recovery after surgery (ERAS) protocol, featuring basiliximab and steroid induction, early mammalian target of rapamycin inhibitor (mTOR) use, and reduced tacrolimus dosing.

Despite varied ICI washout intervals (median 36 days), no AR episodes were observed in any group. One‐year overall survival and recurrence‐free survival were 93%/85% and 100%/85% in standard patients, and 77%/69% in ICI‐exposed patients, respectively. The most frequent complications were biliary and infectious, with no significant intergroup differences.

These findings suggest that in a standardized clinical pathway with structured immunosuppressive protocols, therapeutic drug monitoring, and early complication surveillance, LT can be safely performed after ICI exposure without increasing rejection risk. The study underscores the need for standardized clinical pathways and consistent reporting of immunosuppressive regimens to optimize outcomes in this emerging patient population.