Controlled clinical trials are recognized as the best source of data on the efficacy of health care interventions and technologies. Because economic evaluation is dependent on the quality of the underlying medical evidence, clinical trials have increasingly been viewed as a natural vehicle for economic analysis. However, the closer integration of economic and clinical research raises many methodological issues. This paper discusses these issues in trial design, collection of resource use data, collection of outcome data, and interpretation and extrapolation of results. Some guidelines are suggested for economic analysts wishing to undertake evaluations alongside clinical trials.