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The Patient Protection and Affordable Care Act created the nation's first comprehensive comparative effectiveness research (CER) program. According to some optimistic accounts, CER will revolutionize clinical practice and transform the health care delivery system. But what about public health? There are reasons for concern that it could end up left behind in the new era of comparative effectiveness. This article analyzes the considerable promise and serious limitations of applying CER to public health. It also highlights important issues that will likely emerge for public health law and policy as the health care system transitions to greater reliance on CER.