Background: As their loved ones struggle physically and psychologically with transplant toxicities, FCs of patients undergoing HCT experience substantial distress. We assessed the impact of an inpatient palliative care intervention on FC quality of life (QOL) and mood during their loved ones’ HCT hospitalization. Methods: We conducted a randomized trial of inpatient palliative care integrated with transplant care versus transplant care alone for patients hospitalized for HCT and their FCs. Eligible FCs were identified as a relative or a friend with regular in-person contact with the patient and enrolled within 72 hours of the patient’s HCT admission. The intervention entailed at least twice weekly visits between the patient and palliative care during the transplant hospitalization, and FCs were welcome but not required to be present for these visits. We used the CareGiver Oncology QOL Questionnaire (CarGOQOL) to examine QOL, and the Hospital Anxiety and Depression Scale (HADS) to assess FC mood at baseline and week-2 during HCT hospitalization. We used the two-sample t-test to assess changes in QOL and mood from baseline to week-2. Results: We enrolled 160 patients and 94 (58.8%) FCs (control n = 49, intervention n = 45) between 8/2014 and 1/2016. Study groups did not differ significantly in baseline characteristics or overall FC QOL. At 2 weeks, FCs of patients randomized to the intervention reported improvements compared to those receiving transplant care alone in some QOL domains including better coping (0.23 vs. -0.74, p = 0.02) and handling of finances (0.24 vs. -0.46, p = 0.02) and also reported lower depression symptoms (HADS-Depression: 0.25 vs. 1.80, p = 0.03). No other CarGOQOL domains or HADS-anxiety symptoms were significantly different. Conclusions: Involvement of palliative care for patients hospitalized for HCT leads to improvement in FC depression and some aspects of their QOL. These findings demonstrate the positive impact of inpatient integrated palliative and transplant care extends to FCs of patients with hematologic malignancies undergoing HCT. Clinical trial information: NCT02207322