Introduction: Little is known regarding how to accomplish large-scale health care improvement. Our goal is to improve the quality of chronic disease care in all primary care practices throughout North Carolina. Methods: Methods for improvement include (1) common quality measures and shared data system; (2) rapid cycle improvement principles; (3) quality-improvement consultants (QICs), or practice facilitators; (4) learning networks; and (5) alignment of incentives. We emphasized a community-based strategy and developing a statewide infrastructure. Results are reported from the first 2 years of the North Carolina Improving Performance in Practice (IPIP) project. Results: A coalition was formed to include professional societies, North Carolina AHEC, Community Care of North Carolina, insurers, and other organizations. Wave One started with 18 practices in 2 of 9 regions of the state. Quality-improvement consultants recruited practices. Over 80 percent of practices attended all quarterly regional meetings. In 9 months, almost all diabetes measures improved, and a bundled asthma measure improved from 33 to 58 percent. Overall, the magnitude of improvement was clinically and statistically significant (P = 0.001). Quality improvements were maintained on review 1 year later. Wave Two has spread to 103 practices in all 9 regions of the state, with 42 additional practices beginning the enrollment process. Discussion: Large-scale health care quality improvement is feasible, when broadly supported by statewide leadership and community infrastructure. Practice-collected data and lack of a control group are limitations of the study design. Future priorities include maintaining improved sustainability for practices and communities. Our long-term goal is to transform all 2000 primary-care practices in our state. (Contains 2 tables and 2 figures.)