The United Kingdom Safer Patients Initiative is a large-scale effort to reduce preventable harm in hospitals, including medication errors, health care–associated infections, and cardiopulmonary arrests. Implementation of this program is being conducted according to the principles of continuous quality improvement in collaboration with the Institute for Healthcare Improvement. This mixed methods study evaluates the first phase of the project by soliciting the perceptions of project leaders at four hospitals with the goal of analyzing the local impact of the initiative. Respondents discussed the role of safety culture in facilitating success of the project and identified other local factors that enabled safety improvements.