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Importance Understanding the profitability of pharmaceutical companies is essential to formulating evidence-based policies to reduce drug costs while maintaining the industry's ability to innovate and provide essential medicines. Objective To compare the profitability of large pharmaceutical companies with other large companies. Design, Setting, and Participants This cross-sectional study compared the annual profits of 35 large pharmaceutical companies with 357 companies in the SP 500 Index from 2000 to 2018 using information from