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Safety-net hospitals will continue to play a critical role in the US health care system, as they will need to care for the more than twenty-three million people who are estimated to remain uninsured after the Affordable Care Act is implemented. Yet such hospitals will probably have less federal and state support for uncompensated care. At the same time, safety-net hospitals will need to reposition themselves in the marketplace to compete effectively for newly insured people who will have a choice of providers. We examine how five leading safety-net hospitals have begun preparing for reform. Building upon strong organizational attributes such as health information technology and system integration, the study hospitals' preparations include improving the efficiency and quality of care delivery, retaining current and attracting new patients, and expanding the medical home model.