Recent data suggest that a majority of hospitals now engage in some form of Lean process improvement in an attempt to reduce costs and/or improve quality. The literature on Lean healthcare has evolved from describing theoretical benefits, implementation barriers, and best practices to studies describing where implementations have occurred and their outcomes. Nevertheless, previous studies are mostly limited to case studies in which Lean was implemented on a limited basis in a healthcare facility. In this article, we present lessons learned from the largest implementation of Lean in a single healthcare system composed of 16 hospitals, a health plan, and many outpatient clinics. Our analysis of 1,144 rapid improvement events (RIEs) over a 5-year period revealed that 45% were associated with some organizational benefit in several categories, including cost reductions, time savings, a reduction in clinical and nonclinical defects, and a reduction in workflow steps. As the organization became more experienced with RIEs, the benefits realized changed from mostly cost reductions to a more diverse mix of benefits, with time savings becoming the most common. RIEs implemented in certain settings and/or by certain types of employees were associated with the likelihood of realizing a benefit. Based on these analyses, we provide recommendations to hospital and health system leaders interested in optimizing their Lean implementations-especially on a large enterprise-wide scale.