BACKGROUND The Institute of Medicine's 2001 report Crossing the Quality Chasm argued for fundamental redesign of the U.S. health care system. Six years later, many health care organizations have embraced the report's goals, but few have succeeded in making the substantial transformations needed to achieve those aims. OBJECTIVE This article offers a model for moving organizations from short-term, isolated performance improvements to sustained, reliable, organization-wide, and evidence-based improvements in patient care. METHODS Longitudinal comparative case studies were conducted in 12 health care systems using a mixed-methods evaluation design based on semistructured interviews and document review. Participating health care systems included seven systems funded through the Robert Wood Johnson Foundation's Pursuing Perfection Program and five systems with long-standing commitments to improvement and high-quality care. RESULTS Five interactive elements appear critical to successful transformation of patient care: (1) Impetus to transform; (2) Leadership commitment to quality; (3) Improvement initiatives that actively engage staff in meaningful problem solving; (4) Alignment to achieve consistency of organization goals with resource allocation and actions at all levels of the organization; and (5) Integration to bridge traditional intra-organizational boundaries among individual components. These elements drive change by affecting the components of the complex health care organization in which they operate: (1) Mission, vision, and strategies that set its direction and priorities; (2) Culture that reflects its informal values and norms; (3) Operational functions and processes that embody the work done in patient care; and (4) Infrastructure such as information technology and human resources that support the delivery of patient care. Transformation occurs over time with iterative changes being sustained and spread across the organization. CONCLUSIONS The conceptual model holds promise for guiding health care organizations in their efforts to pursue the Institute of Medicine aims of fundamental system redesign to achieve dramatically improved patient care.