Implementation of large-scale safety improvement programs requires learning organizations—organizations with the capacity for change. The Safer Patients Initiative was implemented at four United Kingdom sites in 2004 in collaboration with the Institute for Healthcare Improvement with the goal of reducing preventable harm. This qualitative study evaluated the readiness of each organization to undertake this initiative, and found that a positive safety culture, a history of organizational leadership and involvement in safety initiatives, and availability of information technology for quality measurement were important predictors of successful implementation. The importance of strong organizational leadership in improving safety was recognized by The Joint Commission in a Sentinel Event Alert.