Background: During HSCT, patients endure significant side effects in the hopes of curing their disease. While many studies have focused on the long-term outcomes of HSCT recipients, the acute impact of hospitalization for HSCT on patients’ QOL and mood is unknown. Furthermore, data on patients’ perception of their prognosis are lacking. Methods: We conducted a prospective longitudinal study of patients hospitalized at Massachusetts General Hospital for HSCT. At baseline and weeks 1, 2, and 3 of hospitalization, we assessed QOL (Functional Assessment of Cancer Therapy- Bone Marrow Transplantation [FACT-BMT]; higher scores indicate better QOL), fatigue (FACT-Fatigue; high scores indicate less fatigue), and mood (Hospital Anxiety and Depression Scale score > 7 on anxiety or depression subscale considered clinically significant). Using a 10-item questionnaire, we measured patients’ information preferences, and perception of their prognosis. Results: We enrolled 60 consecutive patients undergoing autologous (n=30), or myeloablative allogeneic (n=30) HSCT. Patients’ QOL declined and fatigued increased throughout hospitalization [Table 1]. The proportion of patients with depression symptoms increased from baseline to week 3 (18.3% to 33.3%, p=0.002) whereas the proportion of patients with anxiety did not change significantly from baseline (22.6%, p=0.7). Although 90.0% of patients stated that it is ‘extremely’ or ‘very’ important to know about their prognosis, 86.2% reported inaccurate and overly optimistic perception of their prognosis compared to their physicians (p < 0.0001). Conclusions: Patients undergoing HSCT report an overly optimistic perception of their prognosis and experience significant decline in QOL with increasing rates of depression throughout their hospitalization. Interventions to improve QOL, psychological outcomes, and prognostic awareness of patients hospitalized for HSCT are warranted.