BACKGROUND: : Hematopoietic cell transplants (HCTs) are associated with high morbidity and mortality, which complicate the decision-making process for people considering HCT clinical trials. There is a lack of research examining longitudinally how patients make clinical trial participation decisions in US cancer referral centers. OBJECTIVE: : A qualitative study was conducted to examine how patients and their family caregivers decide to participate in HCT research at a US cancer referral center. METHODS: : Semistructured interviews were conducted with 25 patients enrolled in early-stage phase 2 HCT research studies and with 20 family caregivers. Interviews were conducted before HCT and approximately days 80 and 365 after HCT. RESULTS: : Most patients (92%) and their caregivers (75%) decided to participate in research well before consent conferences at the cancer referral center. Patients' reasons for deciding to participate included having "no other option," seeking a cure, and following their home oncologists' recommendations. CONCLUSION: : Currently, US researchers are primarily guided by Federal regulations that view the decision-making process as a cognitive one. Findings confirmed cognition was a part of consent; however, most patients made the decision to participate in high-risk clinical trials long before they had been apprised of the specific information about the study and before the consent conference. IMPLICATIONS FOR PRACTICE: : The high risk of death from the disease and/or the HCT underscored the emotional component of decision making and affirmed that researchers need to acknowledge this emotional component to meet the ethical imperative of providing "informed consent."