Accountable Care Organizations’ (ACOs) pursuit of the triple aim of higher quality, lower cost, and improved population health has met with mixed results. To improve the design and implementation of ACOs we look to organizations that manage similarly complex, dynamic, and tightly coupled conditions while sustaining exceptional performance known as high-reliability organizations. We describe the key processes through which organizations achieve reliability, the leadership and organizational practices that enable it, and the role that professionals can play when charged with enacting it. Specifically, we present concrete practices and processes from health care organizations pursuing high-reliability and from early ACOs to illustrate how the triple aim may be met by cultivating mindful organizing, practicing reliability-enhancing leadership, and identifying and supporting reliability professionals. We conclude by proposing a set of research questions to advance the study of ACOs and high-reliability research.