BACKGROUND: Normothermic machine perfusion (NMP) has emerged as a promising technology in liver transplantation, but limited data exist regarding real-world implementation in the United States following FDA approval. We report our experience establishing an NMP program and share insights from our first 100 cases. METHODS: We retrospectively analyzed 100 consecutive liver NMP cases performed between July 2023 and May 2024 using the OrganOx Metra device. Program establishment required assembling a dedicated team, comprehensive training, establishing a dedicated perfusion facility, coordinating with multiple departments including laboratory, blood bank, electronic medical record vendors, and billing services, and developing institutional viability criteria. RESULTS: Of 100 NMP cases, 92 proceeded to transplantation while eight were declined. Early allograft dysfunction occurred in 19 cases (20.7%) with no instances of primary non-function, and 90-day graft survival was 94.6%. No graft losses were directly attributable to NMP. Six grafts showed delayed lactate clearance but achieved successful outcomes with extended perfusion time. We systematically refined our protocols and developed standardized troubleshooting approaches to address various technical challenges including graft bleeding, arterial flow monitoring issues, persistent acidosis, and bile duct drainage issues. CONCLUSIONS: Successful implementation of an NMP program requires careful preparation, dedicated staffing, and interdepartmental coordination. Although various challenges are expected in the initial phase of the program, these can be successfully managed with a systematic approach. Our experience provides practical guidance for centers planning to establish NMP programs.