Healthcare has enthusiastically embraced quality and safety improvement. Yet, more radical transformation is clearly needed to make a more significant impact on error reduction and to ensure consistent quality. This need for transformation is leading healthcare to examine how other industries, such as nuclear power and aviation, improve safety to achieve a high degree of reliability and avoid potential catastrophes. Research has shown that successful organizations in high-risk industries achieve high reliability by maintaining a cultural mindfulness that allows them to continually reinvent themselves in complex environments. Healthcare faces similar challenges and could greatly benefit from instilling high-reliability principles in its operations. The Medical University of South Carolina, an academic health system, has been on a quest to improve safety and quality by implementing a high-reliability culture.