The purpose of this study was to examine the role of spirituality in terminally ill cancer patients who volunteer for clinical trials of experimental agents. Information about spirituality (FACIT-Sp), quality of life (FACT-G), awareness of prognosis, and decision-making preferences was obtained from 162 advanced cancer patients who volunteered for phase I trials. In a multivariable model, phase I patients had slightly higher levels of spirituality (p<0.001) than a group of 156 advanced cancer patients who were not participants in phase I trials. For the phase I patients, spirituality was positively associated with quality of life (Spearman rho = 0.36, p<0.001). There was little association between either spirituality or religious problem-solving style and phase I patients' awareness of their prognosis or decision-making preferences. One phase I patient who said, ‘I put faith in doctors and God,’ expressed these patients' willingness to trust both God and medicine. Copyright © 2004 John Wiley & Sons, Ltd.