Diagnostic imaging (DI) is the fastest growing sector in medical expenditures and takes a central role in medical decision-making. The increasing number of various and new imaging technologies induces a growing demand for cost-effectiveness analysis (CEA) in imaging technology assessment. In this article we provide a comprehensive framework of direct and indirect effects that should be considered for CEA in DI, suitable for all imaging modalities. We describe and explain the methodology of decision analytic modelling in six steps aiming to transfer theory of CEA to clinical research by demonstrating key principles of CEA in a practical approach. We thereby provide radiologists with an introduction to the tools necessary to perform and interpret CEA as part of their research and clinical practice.