In summary, our **data** provide a comprehensive comparison of large-scale plasma proteomic profiling platforms. The antibody-based platform appears to confer a protein-for-protein edge in specificity and phenotypic association, while the aptamer-based approach demonstrates more reproducible measurements and greater breadth of measurement across the proteome. When choosing a platform, other factors, not directly comparable, may also bear consideration, such as required sample volume, scalability, and cost. Both have provided excellent biological insights in multiple investigations and likely will continue to do so, particularly when profiling with LC-MS, despite notable recent improvement (37), cannot presently provide the necessary sample throughput. Table 2. Lasso regression models in JHS. Lasso regression models are shown for eight phenotypes derived from all proteins available on each platform across 568 samples in JHS. The variance explained by the model and the number of proteins required to achieve that level of variance are shown. FEV1, Forced expiratory volume in the first second. HDL, high-density lipoprotein; ASCVD, atherosclerotic coronary risk score. ASCVD risk score is based on the pooled cohort equation. 