Applying a 3.0 transformation framework to guide large-scale health system reform. Implementation of the Affordable Care Act is unleashing historic new efforts aimed at reforming the US health system. Many important incremental improvements are under way, yet there is a growing recognition that more transformative changes are necessary if the health care system is to do a better job of optimizing population health. While the concept of the Triple Aim-dedicated to improving the experience of care, the health of populations, and lowering per capita costs of care-has been used to help health care providers and health care systems focus their efforts on costs, quality, and outcomes, it does not provide a roadmap for a new system. In this article we describe the 3.0 Transformation Framework we developed to stimulate thinking and support the planning and development of the new roadmap for the next generation of the US health care system. With a focus on optimizing population health over the life span, the framework suggests how a system designed to better manage chronic disease care could evolve into a system designed to enhance population health. We describe how the 3.0 Transformation Framework has been used and applied in national, state, and local settings, and we suggest potential next steps for its wider application and use.