The Organ Donation Breakthrough Collaborative was initiated in April 2003 by Health and Human Services Secretary Tommy G. Thompson and others. The goal of the Collaborative: to dramatically increase access to transplantable organs in the US health care system. The authors describe the system redesign and results achieved using the Collaborative methodology developed by the Institute for Healthcare Improvement. The Collaborative has led to major increases in conversion rates at the participating hospitals as well as to national increases in organ donations.