Abstract Background Chemistry panels play a crucial role in determining a person’s general health and well-being. These tests evaluate electrolyte balance and the status of several major organs. The Comprehensive Metabolic Panel (CMP) and Lipid Panel constitute approximately 87% of the blood tests prescribed in medical laboratories. Laboratories monitor assay performance by performing proficiency testing using quality controls (QC). College of American Pathologists (CAP) data is useful for laboratories to compare their proficiency testing performance to other laboratories and instrument systems. Sigma metrics serve as a valuable tool for laboratories to assess the quality and accuracy of their tests. Sigma scores vary from 0 to 6, with the 6 score designated as world-class performance, 5 as excellent, 4 as good, 3 as marginal, and 2 as poor. The analytical performance of 16 clinical assays from Abbott, Beckman, Roche, and Siemens instrument systems were compared using Sigma metrics. Methods Sigma metrics of 16 chemistry analytes were compared across 4 instruments system using CAP data from three reports (C-A 2023, C-C 2023 and C-B 2022). The 4 systems evaluated were Abbott Alinity ci, Beckman AU, Roche COBAS c500/c303 and Siemens Atellica CH. Method imprecision was estimated for each assay using the cumulative coefficient of variation or standard deviation for each assay at a single QC concentration and calculating the average sigma. Since sigma levels can be concentration-dependent, an equivalent CAP sample concentration was chosen for each instrument system evaluation. Method bias was estimated by evaluating each method QC mean to the peer group mean. Sigma values were calculated for each method as Sigma = (TEa - |Bias|) / Precision using the allowable total error from 2014 Clinical Laboratory Improvement Amendments (CLIA) proposed acceptance limits. Average Sigma values were generated for each analyte and graded as an optimal Sigma score. Results The sigma scores varied across assays and instrument systems. Abbott demonstrated the best overall performance. Specifically, the Abbott Alinity system had the highest number (7/16, 44%) of assays at 5 sigma or higher, with Siemens showing the lowest number of assays at 5 Sigma or higher (1/16, 6%). Of the 16 assays evaluated, Abbott has the fewest assays at or below the 3 sigma threshold (5/16) when compared to Roche (7/16), Beckman (7/16), and Siemens (9/16). Sigma scores were comparable between the Abbott ARCHITCT and Alinity clinical chemistry systems. Conclusions Sigma metrics are useful in assessing the performance of clinical assays. Assays with high Sigma have better performance due to lower imprecision and higher accuracy. None of the instrument systems demonstrated optimal six sigma performance for all analytes. However, Abbott demonstrated the best overall performance.