Medication reconciliation is necessary to reduce preventable medication errors, but despite much research, no consensus exists on how the process should be performed in either the inpatient or outpatient setting. This study, conducted at a children's hospital, demonstrates how accurate medication reconciliation can be achieved through establishing a culture of safety and rigorously applying quality improvement principles. Although the hospital had an existing electronic health record and computerized provider order entry system, a reliable medication reconciliation process was not achieved until existing processes were thoroughly analyzed, failure modes were determined, and rapid cycle tests of change were conducted. As medication reconciliation will be reinstated as a National Patient Safety Goal in July 2011, this article provides a useful blueprint for organizations tackling this difficult problem.