Background: Widespread adoption of information and communication technologies (ICT) is a key strategy to meet the challenges facing health systems internationally of increasing demands, rising costs, limited resources and workforce shortages. Despite the rapid increase in ICT investment, uptake and acceptance has been slow and the benefits fewer than expected. Absent from the research literature has been a multi-site investigation of how ICT can support and drive innovative work practice. This Australian-based project will assess the factors that allow health service organisations to harness ICT, and the extent to which such systems drive the creation of new sustainable models of service delivery which increase capacity and provide rapid, safe, effective, affordable and sustainable health care. Design. A multi-method approach will measure current ICT impact on workforce practices and develop and test new models of ICT use which support innovations in work practice. The research will focus on three large-scale commercial ICT systems being adopted in Australia and other countries: computerised ordering systems, ambulatory electronic medical record systems, and emergency medicine information systems. We will measure and analyse each system's role in supporting five key attributes of work practice innovation: changes in professionals' roles and responsibilities; integration of best practice into routine care; safe care practices; team-based care delivery; and active involvement of consumers in care. Discussion. A socio-technical approach to the use of ICT will be adopted to examine and interpret the workforce and organisational complexities of the health sector. The project will also focus on ICT as a potentially disruptive innovation that challenges the way in which health care is delivered and consequently leads some health professionals to view it as a threat to traditional roles and responsibilities and a risk to existing models of care delivery. Such views have stifled debate as well as wider explorations of ICT's potential benefits, yet firm evidence of the effects of role changes on health service outcomes is limited. This project will provide important evidence about the role of ICT in supporting new models of care delivery across multiple healthcare organizations and about the ways in which innovative work practice change is diffused.