Over the past twenty years, important changes in the Italian health system have led to different approaches in organizing, delivering and financing health services throughout the country's regions. In this paper, we assess the impacts that such changes have had on health efficiency. The analysis performed here is in two stages. In the first stage, healthcare efficiency is measured via bootstrapped Data Envelopment Analysis. In the second stage, the impacts of organizational and environmental variables on efficiency are investigated. Our results highlight that the organizational model adopted by the Lombardia region allows for the best results in healthcare efficiency in Italy. A process of administrative decentralization from the regional governments to local health units appears to be a source of inefficiency. Finally, patient mobility has a significant impact on healthcare efficiency. Copyright © 2013 John Wiley & Sons, Ltd.