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<h3>Objectives</h3> Laboratory testing that exceeds evidence-based recommendations contributes to overdiagnosis, unnecessary downstream procedures, and substantial financial waste. Until recently, the magnitude of this issue at a national level remained poorly quantified. We aimed to measure the prevalence and cost of inappropriate laboratory testing in the United States by analyzing an exceptionally large dataset of paid insurance claims. Our study examined over 1 billion outpatient laboratory claims from 2019, covering approximately 232 million individuals—more than 91% of the U.S. adult population. The primary objective was to quantify testing that exceeded published guidelines and estimate the associated waste. We focused on a subset of commonly used tests with clearly defined recommendations for testing frequency. This analysis (Smart et al., Arch Pathol Lab Med, 2024; doi:10.5858/arpa.2023-0486-OA) provides new insights into low-value care at scale and highlights actionable opportunities for stakeholders to reduce overuse, subsequent overdiagnosis, and reallocate resources toward higher-value, evidence-based care. <h3>Method</h3> We conducted a retrospective analysis of 2019 U.S. outpatient paid laboratory claims from Medicare and multiple commercial payers. The dataset included over 1 billion test records, representing 64 million Medicare beneficiaries and 168 million individuals with commercial insurance. The year 2019 was intentionally selected to avoid the distortions in healthcare utilization caused by the COVID-19 pandemic; a targeted analysis of 2022 data confirmed that 2019 trends persisted. We selected four commonly used laboratory tests—25-hydroxy vitamin D, prostate-specific antigen (PSA), lipid panel, and hemoglobin A1c—based on the availability of well-defined clinical guidelines for testing frequency. Costs of excessive testing were calculated using the 2019 U.S. Medicare Clinical Laboratory Fee Schedule. Processing 1.84 billion rows of Medicare claims alone required substantial computational resources and infrastructure, underscoring the technical complexity of conducting large-scale, high-resolution analyses of healthcare overuse. <h3>Results</h3> Among 84 million tests analyzed, 7% to 51% exceeded recommended testing frequencies—ranging from 7% for lipid panels to 51% for 25-hydroxy vitamin D, with hemoglobin A1c (30%) and PSA (27%) in between. Smaller fractions exhibited egregious patterns—for example, monthly testing of hemoglobin A1c or PSA. Among 60.5 million individuals who received at least one of the four tests, 14.4 million (24%) underwent at least one test more frequently than recommended. The conservative cost estimate for overuse of these four tests exceeded $350 million. When extrapolated across all outpatient lab testing, Medicare alone may have incurred $1.95 to $3.28 billion in excess costs in 2019. A focused analysis of 2022 claims confirmed that overuse trends persisted beyond the pandemic. Our findings reveal both the breadth and persistence of low-value testing across Medicare and commercial payers. <h3>Conclusions</h3> Inappropriate laboratory testing is systemic, costly, and potentially harmful. From the patient perspective, it imposes out-of-pocket costs (copays, coinsurance, self-pay), time burdens, and emotional distress from marginally out-of-range results. Additional burdens may include unnecessary physician visits, blood draws, and follow-up testing. Clinically, laboratory overuse increases the risk of false positives and cascades of unnecessary care, including imaging, procedures, specialist referrals and hospital admissions. Meanwhile, resources wasted on testing with low clinical value could be redirected to address gaps in care for populations that remain systematically undertested. Addressing this preventable overuse will require coordinated efforts—policy reforms, aligned payer-laboratory incentives, targeted clinical decision support, and greater awareness among both clinicians and patients.