The goal of high-reliability organizations is to operate in high-hazard domains with consistently safe conditions, but implementation of high reliability has yet to be universally employed in health care. This article describes the implementation of a high-reliability hospital framework on patient safety culture and clinical outcomes at one VHA medical center. Framework components included an annual patient safety assessment, annual safety culture survey, annual root cause analysis (RCA) training, leadership walk arounds, and just culture training. Three years after implementation, patient safety culture and event reporting rates improved, and the medical center experienced significant improvements in mortality and complication rates compared to other VHA hospitals. Based on these results, the framework will be implemented across 18 additional VHA sites.