Economic evaluation in health care supports decision makers in prioritizing interventions and maximizing the available limited resources for social benefits. Health Information Technology (health IT) constitutes a promising strategy to improve the quality and delivery of health care. However, to determine whether the appropriate health IT solution has been selected in a specific health context, its impact on the clinical and organizational process, on costs, on user satisfaction as well as on patient outcomes, a rigorous and multidimensional evaluation analysis is necessary. Starting from the principles of evaluation introduced since the mid-1980s within the Health Technology Assessment (HTA) guidelines, this contribution provides an overview of the main challenging issues related to the complex task of performing an economic evaluation of health IT. A set of necessary key principles to deliver a proper design and implementation of a multidimensional economic evaluation study is described, focusing in particular on the classification of costs and outcomes as well as on the type of economic analysis to be performed. A case study is eventually described to show how the key principles introduced are applied.