Health systems are increasingly aiming to become high-reliability organizations, able to operate for an extended period without serious accidents. This systematic review identified 75 studies reporting on health systems’ interventions to improve reliability, the goals of the interventions, and how achievement of the goals was measured. The six goals of Crossing the Quality Chasm were used to categorize studies. Most studies focused solely or in part on safety; only ten focused solely on one of the other five goals.