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We conducted the first profitability comparison study across health care industries in the United States, using the DuPont Analysis framework. The combination of Return on Equity (ROE) and ROE volatility was used to provide a comprehensive "risk-return" approach for profitability comparison. Based on the 2010-2019 financial disclosures of 1,231 publicly traded health care companies in the U.S. that reported positive assets and equity, we estimated the industry-specific fixed effects on ROE and its three components-profit margin, asset utilization, and financial leverage-for ten industries in the health care sector, classified by the Global Industry Classification Standard (GICS). For each industry, we also estimated its fixed effects on ROE volatility. We found that the pharmaceuticals industry and biotechnology industry have lower ROE-mainly driven by their relatively low profit margin and low assets utilization-and higher ROE volatility than other health care industries. We also found that the health care facilities industry relies most on debt financing. This study demonstrates a holistic approach for profitability comparison across industries., Competing Interests: The authors have read the journal’s policy and have the following competing interests: GB received funding from Arnold Ventures, LLC unrelated to this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)