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Background: Given the current organ shortage crisis, split liver transplantation (SLT) has emerged as a promising alternative for select end-stage liver disease patients., Aim: To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT., Methods: A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1, 2022, and May 31, 2023. The study included 25 SLT cases and 81 whole liver transplantation (WLT) cases. Total ex-vivo liver splitting was employed for SLT graft procurement in three steps. Patient outcomes were determined, including liver function parameters, postoperative complications, and perioperative mortality. Group comparisons for categorical variables were performed using the χ² -test., Results: In the study, postoperative complications in the 25 SLT cases included hepatic artery thrombosis ( n = 1) and pulmonary infections ( n = 3), with no perioperative mortality. In contrast, among the 81 patients who underwent WLT, complications included perioperative mortality ( n = 1), postoperative pulmonary infections ( n = 8), abdominal infection ( n = 1), hepatic artery thromboses ( n = 3), portal vein thrombosis ( n = 1), and intra-abdominal bleeding ( n = 5). Comparative analysis demonstrated significant differences in alanine aminotransferase (176.0 vs 73.5, P = 0.000) and aspartate aminotransferase (AST) (42.0 vs 29.0, P = 0.004) at 1 wk postoperatively, and in total bilirubin (11.8 vs 20.8, P = 0.003) and AST (41.5 vs 26.0, P = 0.014) at 2 wk postoperatively. However, the overall incidence of complications was comparable between the two groups ( P > 0.05)., Conclusion: Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach, especially under the expertise of an experienced transplant center. The approach developed by our center can serve as a valuable reference for other transplantation centers., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interests or disclosures to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)