Private- and public-sector initiatives, using electronic health record (EHR) databases from millions of people, could rapidly advance the U.S. evidence base for clinical care. Rapid learning could fill major knowledge gaps about health care costs, the benefits and risks of drugs and procedures, geographic variations, environmental health influences, the health of special populations, and personalized medicine. Policymakers could use rapid learning to revitalize value-based competition, redesign Medicare's payments, advance Medicaid into national health care leadership, foster national collaborative research initiatives, and design a national technology assessment system.