Abstract Background The DxC 500i Clinical Analyzer* is Beckman Coulter’s latest integrated Clinical Chemistry and Immunoassay analyzer. It provides reliability, scalability, and workflow efficiency via a flexible independent maintenance mode, increased uptime, and a dynamic sample handler to optimize sample management. Standard Beckman Coulter Chemistry and Immunoassay consumables and reagents ensure network standardization and commutability. The purpose of this study was to evaluate the analytical performance of the new DxC 500i analyzer and to compare the performance against the Beckman Coulter stand-alone Clinical Chemistry and Immunoassay analyzers on the market. Methods To assess performance over a range of assay methodologies, several DxC 500i Beckman Coulter Immunoassays and Chemistry assays were evaluated. Precision was assessed using human samples following CLSI EP05-A3 guidelines. Linear range was assessed following CLSI EP06-A guidelines. Method Comparison and Bias Estimation studies compared the DxC 500i Clinical Analyzer against the Access 2 Immunoassay System, the AU480 and the DxC 700 AU Clinical Chemistry analyzers, following CLSI EP09c-ED3 guidelines. To investigate carryover potential as samples are processed across the integrated system, a carryover study was designed. This focused on evaluating potential sample-to-sample carryover caused by the AU sample probe and its effects on immunoassay samples during reflex scenarios. Results DxC 500i Chemistry results: Glucose Serum (OSR6x21) Assessments of repeatability and within laboratory precision at multiple critical analyte concentrations showed total imprecision of <3% and within-run imprecision of <3%. The Glucose serum assay demonstrated acceptable linearity throughout the 10-800 mg/dL analytical measuring range. Method comparison studies compared the DxC 500i analyzer against the AU480 and DxC 700 AU systems. A Weighted Deming regression of serum patient samples (n>100 measured across the analytical range) yielded a 0.986 slope, 0.227 mg/dL intercept, and R=0.9999 correlation coefficient against the DxC 700 AU and a 0.995 slope, 0.356 mg/dL intercept, and R=0.9999 correlation coefficient against the AU480. DxC 500i Immunoassay results: Cortisol (33600) Beckman Coutler’s Cortisol assay exhibited total imprecision of <12%CV at <5 μg/dL or <10CV% at ≥5 μg/dL for serum. The Cortisol assay demonstrated acceptable linearity throughout the 0.4-60 μg/dL analytical measuring range. A method comparison study compared the DxC 500i against the Access 2 system. A Weighted Deming regression of serum patient samples (n>100 measured across the analytical range) yielded a 0.9785 slope, 0.2764 μg/dL intercept, and R=0.9932 correlation coefficient. DxC 500i Carryover Assessment The Total βhCG (5th IS) assay was used to evaluate the potential of chemistry analyzer to immunoassay analyzer sample carryover. The study used High hCG serum samples (>1,000,000 mIU/mL) and Low hCG serum samples (4-6 mIU/mL). The DxC 500i exhibited a cumulative carryover of ≤2 parts per million (PPM) for serum. Conclusions These studies demonstrate excellent analytical performance for the new Beckman Coulter DxC 500i Clinical Analyzer* and confirm comparable performance to current Beckman Coulter standalone Clinical Chemistry and Immunoassay analyzers on the market. *Pending clearance by the United States Food and Drug Administration; not yet available for in vitro diagnostic use in the U.S. Product availability and regulatory status depends on country registration per applicable regulations.