Delirium commonly occurs during myeloablative hematopoietic cell transplantation (HCT). Little is known about how delirium during the acute phase of HCT affects long-term distress, health-related quality of life (HRQOL), and neurocognitive functioning. This prospective, cohort study examines these outcomes at 6 months and 1 year in 90 patients undergoing HCT. Patients completed a battery assessing distress, HRQOL, and subjective neuropsychological functioning before receiving their first HCT as well as at 6 months and 1 year. Patients with a delirium episode within the 4 weeks after HCT had significantly more distress and fatigue at 6 months (P < .004) and at 1 year (P < .03), compared with patients without delirium. At 1 year, patients with delirium also had worse symptoms of depression and post traumatic stress (P < .03). Patients with delirium had worse physical health on the SF-12 at 6 months (P < .03) and worse mental health on the SF-12 at 1 year (P < .03). At both 6 months and 1 year, patients with delirium after HCT reported worse memory (P < .009) and executive functioning (P < .006). Delirium during the acute phase of HCT is significantly associated with persistent distress, decreased HRQOL, and subjective neurocognitive dysfunction at both 6 months and 1 year.