The Reconditioning Exercise and Chronic Obstructive Pulmonary Disease Trial (REACT) is a two-arm randomized clinical trial designed to compare short-term versus long-term exercise intervention in terms of physical function, acute exacerbation of chronic obstructive pulmonary disease, health-related quality of life, and cost-effectiveness. Clinical trials such as REACT are now routinely paired with economic analyses, and nurses can expect to play a growing role in the conduct of these studies. This article describes a model that is useful for structuring economic evaluations of health care interventions, and illustrates a cost-effectiveness analysis that is being conducted in conjunction with the REACT study. An in-depth description of collection methods and procedures is provided, as well as a summary of recruitment and retention experience to date.