Our goal was to compare direct and indirect medical costs and quality of life associated with inpatient vs outpatient autologous hematopoietic stem cell transplantation (AuHSCT). Twenty-one sequential outpatients and 26 inpatients were enrolled on this prospective trial. All candidates for AuHSCT were screened for eligibility for outpatient transplantation. Patients with either breast cancer or hematologic malignancy, insurance coverage for the outpatient procedure, one to three caregivers available to provide 24 h coverage, and no significant comorbidities were eligible to participate. Patients without caregivers or insurance coverage for outpatient transplant were accrued to the study in a consecutive manner as inpatient controls, based on willingness to participate in the quality of life portion of the study and to permit review of their hospital and billing records. Approximately half of all 139 prospective outpatient candidates were ineligible because they lacked a caregiver. Most commonly, the patient without a caregiver was single or widowed or their family and friends were needed to provide childcare. Most caregivers were college educated from families with incomes greater than US dollars 80000. Indirect costs to the caregivers totaled a median of US dollars 2520 (range US dollars 684-US dollars 4508), with the majority attributed to lost 'opportunity costs'. Overall, there were significant differences in the total costs of treatment for inpatient vs outpatient AuHSCT (US dollars 40985 vs US dollars 29210, P < 0.01)). In general, no significant differences were detected between inpatient and outpatient scores on quality of life measures. Although significant cost savings were associated with outpatient transplantation, this approach was applicable to only half of our otherwise eligible candidates because of a lack of caregivers. The financial burden associated with the caretaking role may underlie this finding.