Organizational culture change is often touted as the key to achieving high reliability in health care. Culture is also associated with quality improvement collaboratives' success in reducing preventable harm, such as avoidable readmissions or myocardial infarction (MI) mortality. In this mixed-methods longitudinal study, investigators prospectively ascertained how 10 hospitals changed their culture while participating in the Leadership Saves Lives program. Hospitals who appointed diverse guiding coalitions, promoted genuine team member engagement, and managed conflict successfully exhibited both significant culture change and larger reductions in 30-day MI mortality. This study enriches knowledge about how hospital leaders can promote sustained improvement. A Patient Safety Primer and PSNet perspective elaborate how to engage in prioritizing safety as a leader.