Background: The approach and style of leaders is known to be an important factor influencing the translation of research evidence into nursing practice. However, questions remain as to what types of roles are most effective and the specific mechanisms through which influence is achieved. Objectives: The aim of the study was to enhance understanding of the mechanisms by which key nursing roles lead the implementation of evidence-based practice across different care settings and countries and the contextual factors that influence them. Design: The study employed a qualitative descriptive approach. Settings: Data collection was undertaken in acute care and primary/community health care settings in Australia, Canada, England and Sweden. Participants: 55 individuals representing different levels of the nursing leadership structure (executive to frontline), roles (managers and facilitators), sectors (acute and primary/community) and countries. Methods: Individual semi-structured interviews were conducted with all participants exploring their roles and experiences of leading evidence-based practice. Data were analysed through a process of qualitative content analysis. Results: Different countries had varying structural arrangements and roles to support evidence-based nursing practice. At a cross-country level, three main themes were identified relating to different mechanisms for enacting evidence-based practice, contextual influences at a policy, organisational and service delivery level and challenges of leading evidence-based practice. Conclusions: National policies around quality and performance shape priorities for evidence-based practice, which in turn influences the roles and mechanisms for implementation that are given prominence. There is a need to maintain a balance between the mechanisms of managing and monitoring performance and facilitating critical questioning and reflection in and on practice. This requires a careful blending of managerial and facilitative leadership. The findings have implications for theory, practice, education and research relating to implementation and evidence-based practice.