Background Lean practices have been widely used by health care organizations to meet efficiency, performance and quality improvement needs. The lean health care literature shows that the effective implementation of lean requires a holistic system-wide approach. However, there is still limited evidence on what drives effective system-wide lean implementation in health care. The existing literature suggests that a deeper understanding of how lean interventions interact with the organizational context is necessary to identify the critical variables to successfully sustain system-wide lean strategies. Purpose and methodology: A multiple case study of three Italian hospitals is conducted with the aim to explore the organizational conditions that are relevant for an effective system-wide lean implementation. A conceptual framework, built on socio-technical system schemas, is used to guide data collection and analysis.The analysis points out the importance to support lean implementation with an integrated and coordinated strategy involving the social, technical, and external components of the overall hospital system.