Background: Recent analysis of National Get-with-the-Guidelines data has shown that less than one third of all patients treated with intravenous tissue plasminogen activator (tPA) had door-to-needle times (DTN) within the ‘Golden Hour’ recommended by current guidelines. Accumulating evidence indicates that shorter DTN is associated with improved outcomes. In March 2011, we began a fundamental transformation, employing Toyota Lean manufacturing principles to improve Emergency Department (ED) DTN in acute ischemic stroke (AIS) patients receiving IV tPA. Methods: A multi-disciplinary team of ED physicians, Neurologists, Radiologists, Nurses, Patient Care Technologists, Radiology Technologists and Lean Performance Management Engineers critically analyzed the chain of events required to evaluate and treat AIS patients with intravenous tPA. A “current state” value stream Map (VSM) was created to identify barriers and inefficiencies in the process. To address the identified inefficiencies, a “future state” VSM was created and implemented. Time metrics were prospectively collected prior to and after implementation of the “future state” VSM. Results: The “current state” VSM identified several barriers to rapid evaluation for treatment, including: 1) Inefficient patient flow, requiring patients to be routed by EMS to an ED room, then to CT, then back to the room; 2) Redundant procedures (patient was initially hooked up to cardiac monitors, then removed, and re-hooked up after imaging); 3) Serial processing of multiple tasks; 4) Inefficient use of available staff; 5) Difficulties locating witnesses to determine time of onset (TOO); 6) Delays due to laboratory sample processing; 7) Delays due to non-uniform organization of supplies within each room. A “future state” VSM was created, addressing many of the identified inefficiencies: 1) Patients were routed directly to the CT scanner by EMS; 2) A formal team of 6 members was created to initiate work after the stroke pager activation; 3) Each team member was assigned pre-arranged tasks (e.g. social worker to identify and contact witnesses to determine TOO, alternation of NIHSS and medical history duties between EM and Neurology); 4) Point of care tests were implemented for labs that were critical to the decision-making process; 5) Patient registration occurred in the CT suite. Median DTN prior to the “future state” VSM (N=132) was 60 min; after implementation (N=37), median DTN decreased to 37 min (0<0.0001). Initial safety, outcomes data and mimic treatments were statistically insignificant. Conclusion: Lean manufacturing principles can successfully be applied to improve stroke care in an acute hospital setting. We show in this study that DTN times can be dramatically reduced after a Lean intervention. Future analysis will be needed to examine if this intervention is safe, sustainable and leads to improved outcomes.