Background Understanding lipoprotein (a) [Lp(a)] measurement variability is essential in establishing its coronary heart disease (CHD) association, and optimising assessment and management of atherosclerotic cardiovascular disease (ASCVD) risk. We established the components of biological variation (BV) and reference change value (RCV) of Lp(a) in a UK cohort. Method 22 healthy individuals were recruited to the study. Blood samples were collected for six consecutive weeks and analysed in duplicate using the Lp(a) assay by Sentinel Diagnostics on the Beckman Coulter AU5800. Outlier, heterogeneity, normality, and trend analysis were performed, followed by CV-ANOVA to determine estimates of BV, adhering to the 14 BIVAC quality items. RCV was calculated based on estimated CVA and CVI. Results Four participants were excluded from the analysis as their mean Lp(a) levels fell below the functional sensitivity of the assay. Mean Lp(a) concentration ranged from 14 - 241 nmol/L. The overall estimate of CVI for all participants was 10.9% (95% CI of 9.1 - 13.0%). The RCV for Lp(a) was +31.6%/-24.0%. Conclusion Our study obtained a CVI estimate for Lp(a) that aligned consistently with recent studies adhering to the quality specifications outlined in the BIVAC checklist. The CVI estimate was significantly lower than Lp(a) estimates reported in studies up to 2003. The CVI estimate highlights the limitations of relying solely on a single Lp(a) measurement for prognosticating ASCVD risk and identifying candidates for novel Lp(a) therapies, particularly when the measured value is near clinical decision thresholds.