Both economic and clinical evaluations of new pharmaceutical agents are important to physicians who practice in the current health care environment. While cooperative cancer groups carry out large-scale phase III clinical evaluations of these agents, few cooperative group studies incorporate economic analyses because of concerns over overburdening of data management, investigators, and statistical center personnel. In this study, we describe the results and operational considerations of one of the first completed economic analyses of a phase III cooperative group trial of the Eastern Cooperative Oncology Group (ECOG). We developed an economic model estimating economic benefits of yeast-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjunct therapy for adult patients (56-70 years) with acute myelogenous leukemia. Clinical data were based on prospectively collected information from a recently reported double-blind phase III multi-institutional study carried out by ECOG. Retrospective economic data were obtained from financial information systems at our hospital, one of the study sites. The cost-minimization analyses were based on the perspective of a third-party payer. Indirect costs related to loss of earnings by patients and caregivers as well as quality-of-life adjustments were not incorporated into the model. Clinical trial results indicated that patients treated with GM-CSF had shorter times to recovery of absolute neutrophil count of 500 cells/mm3 and 1000 cells/mm3 and fewer serious infections than patients who received placebo following induction chemotherapy, while no significant differences were noted in red blood cell and platelet transfusion dependency, toxicities, and duration of hospitalization. The economic model estimated that the group treated with GM-CSF was estimated to have lower costs of care, associated with lower frequencies of serious infections and lower overall infection-related costs. Sensitivity analyses indicated that these results held true over a wide range of estimates of costs and infection rates. Prospective economic analyses of phase III cooperative cancer group clinical trials have not been completed to date. Strategies that are not likely to overburden data managers and statistical center personnel are possible to devise. However, these studies require careful planning and coordination between clinical trialists, economists, and health services researchers.