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Implementation of polygenic risk scores (PRS) may improve disease prevention and management but requires the construction and validation of clinical assays, interpretation, and reporting pipelines. We developed a clinical genotype array-based assay for published PRS for 6 common diseases. First, we calculated PRS for 36,423 Mass General Brigham Biobank (MGBB) participants. Finding significant variation in the PRS distributions by race, we implemented adjustment for population structure with ancestry-informative principal components. We replicated published thresholds for odds ratio (OR)>2 in MGBB overall [ranging from 1.75 (1.57, 1.95) for Type 2 diabetes to 2.38 (2.07, 2.73) for breast cancer]. After confirming the high performance and robustness of the pipeline for use as a clinical assay, we analyzed the first 141 prospective samples from the Genomic Medicine at VA Study; frequency of PRS corresponding to published OR>2 ranged from 5/141 (3.6%) for colorectal cancer to 8/48 (16.7%) for breast cancer. Our development of a clinical PRS assay for multiple conditions illustrates the generalizability of this process and necessary technical and reporting decisions for meaningful clinical PRS implementation.