Background: During hospitalization for HCT, patients experience physical and psychological symptoms that contribute to a substantial deterioration in their quality of life (QOL). Palliative care is rarely consulted to assist with symptom management in patients with hematologic malignancies. We assessed the impact of an inpatient palliative care intervention on patient-reported QOL, mood, and symptom burden during hospitalization for HCT. Methods: We randomly assigned 160 patients with hematologic malignancies admitted for autologous or allogeneic HCT to an inpatient palliative care intervention (n = 81) integrated with standard transplant care compared to standard transplant care alone (n = 79). We used the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) to assess QOL, the Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire (PHQ-9) to assess mood, and Edmonton Symptom Assessment Scale (ESAS) to measure symptom burden at baseline and week-2 of HCT hospitalization. We compared changes in patient’s QOL, mood, and symptom burden from baseline to week-2 between the study arms using a two-sample t-test. Results: Between 8/1/2014 and 1/15/2016, we enrolled 160/186 (86%) of potentially eligible patients undergoing HCT. Patients randomized to the palliative care intervention (vs. control) reported less decline in QOL (-14.7 vs. -21.5, P = 0.04), and less increase in depression symptoms (HADS-Depression: 2.4 vs. 3.9, P = 0.02), and symptom burden (ESAS: 30.3 vs. 38.3, P = 0.007) from baseline to week-2. Intervention participants reported a decline in anxiety symptoms compared to control patients who reported an increase in anxiety from baseline to week-2 (HADS-Anxiety: -0.80 vs. 1.1, P = 0.0006). There were no significant differences in PHQ-9 between the study arms. Conclusion: Palliative care improved QOL, decreased depression, anxiety, and symptom burden in patients with hematologic malignancies hospitalized for HCT. Involvement of palliative care for patients with hematologic malignancies can improve their outcomes and substantially reduce the physical and psychological burden experienced during HCT. Clinical trial information: NCT02207322