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Objectives: This study compared the new high-volume blood coagulation analyzer Sysmex CS-5100 System™ (Siemens Healthcare Diagnostics, Erlangen, Germany) to the mid-volume blood coagulation analyzer Sysmex CS-2000i System™ (Siemens) for analytical performance. Additionally, the operational performance of the Sysmex CS-5100 System was compared with the blood coagulation analyzer ACL TOP 700 (Instrumentation Laboratory, Werfen Group, Kirchheim bei Munchen, Germany). Materials and methods: We compared the Sysmex CS-5100 to the Sysmex CS-2000i and the ACL TOP analyzer for routine coagulation, chromogenic and immunological assays. Imprecision studies were performed for the Sysmex CS-5100 and Sysmex CS-2000i systems. A throughput and STAT analysis comparison of the CS-5100 and the ACL TOP was performed. A stress test was performed to characterize the robustness and the error rate of the CS-5100. We also performed correlation analysis between the CS-5100 and the CS-2000i or the ACL TOP in the measurement of patients’ samples. Results: The inter-assay precision using the CS systems was impressive (inter-assay CV generally