Improving Performance in Practice (IPIP) is a large system intervention designed to align efforts and motivate the creation of a tiered system of improvement at the national, state, practice, and patient levels, assisting primary-care physicians and their practice teams to assess and measurably improve the quality of care for chronic illness and preventive services using a common approach across specialties. The long-term goal of IPIP is to create an ongoing, sustained system across multiple levels of the health care system to accelerate improvement. IPIP core program components include alignment of leadership and leadership accountability, promotion of partnerships to promote health care quality, development of attractive incentives and motivators, regular measurement and transparent sharing of performance data, participation in organized quality improvement efforts using a standardized model, development of enduring collaborative improvement networks, and practice-level support. A prototype of the program was tested in 2 states from March 2006 to February 2008. In 2008, IPIP began to spread to 5 additional states. IPIP uses the leadership of the medical profession to align efforts to achieve large-scale change and to catalyze the development of an infrastructure capable of testing, evaluating, and disseminating effective approaches directly into practice. (Contains 3 figures and 1 table.)