The National Patient Safety Foundation issued these guidelines for improving root cause analyses (RCAs) in health care organizations. RCAs are mandated by The Joint Commission following sentinel events and many states require them after reports of serious events. A panel of experts and stakeholders created these guidelines, which emphasize the importance of actions taken in response to RCA reviews to prevent future harms. They have proposed renaming the process root cause analysis and action (RCA²) to ensure that efforts will result in the implementation of sustainable systems-based improvements. The document provides strategies for applying efficient and effective RCAs, and it includes tools for evaluating RCA reviews. A prior AHRQ WebM&M perspective examined the application of RCAs for patient safety.