The concentration of health care expenditures has important implications for managing risk pools, drug benefit design, and care management. To examine trends in the concentration of health care spending in different population groups and expenditure categories in the US between 2001 and 2018. This study is a cross-sectional analysis of Medical Expenditure Panel Surveys (MEPS) collected between 2001 and 2018. The MEPS is a household survey of medical expenditures weighted to represent national estimates in the US. Respondents were a nationally representative sample of the US civilian noninstitutionalized population. Data analysis was performed from December 2020 to February 2021. The main outcome is the concentration of health care expenditures as measured by the cumulative percentage of health expenditure vs percentage of ranked population. This study reports trends in the distribution of populations across 4 concentration curve parameters: top 50% expenditure (high spenders), next 49% expenditure (medium spenders), next 1% expenditure (low spenders), and nonspenders. The mean sample size of the MEPS surveys used in the analysis was 34 539 individuals, and the sample size varied between 30 461 and 39 165 individuals over the years studied. On the basis of data from 30 461 MEPS respondents (15 867 women [52.1%]; mean [SD] age, 38.9 [24.0] years) in 2018, the top 4.6% (95% CI, 4.3%-4.9%) of the US population by spending accounted for 50% of health care expenditures. Although this fraction varied across population groups or expenditure categories, it remained remarkably stable over time with one exception: the concentration of spending on prescription drugs. In 2001, one-half of all expenditures on prescription drugs were concentrated in 6.0% (95% CI, 5.6%-6.4%) of the US population, but by 2018, this proportion had decreased to 2.3% (95% CI, 2.1%-2.5%). This change does not appear to be associated with a change in the overall share of prescription drug expenses, which increased by only a small amount, from 20.4% in 2001 to 24.8% in 2018. The overall concentration of health care expenditures remained stable between 2001 and 2018, but these findings suggest that there has been a sharp increase in the concentration of spending on prescription drugs in the US. This coincides with the genericization of many primary care drugs, along with a shift in focus of the biopharmaceutical industry toward high-cost specialty drugs targeted at smaller populations. If this trend continues, it will have implications for the minimum scale of risk-bearing and drug management needed to operate efficiently, as well as the optimal cost-sharing features of insurance products.