BACKGROUND: Psychological interventions reduce caregiver distress (CG-distress). Less distress in caregivers may contribute to improved patient quality of life (QoL), but empirical evidence is lacking. Will a caregiver stress management intervention improve patient QoL? METHODS: In this replication study, we randomized 155 allogeneic hematopoietic stem cell transplant (Allo-HSCT) patients and caregivers to PsychoEducation, Paced Respiration, and Relaxation (PEPRR) or enhanced treatment as usual (eTAU). We provided PEPRR over 3 months following transplant. Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) evaluated patient QoL, and CG-distress was based on depressive, anxious, and stress symptoms. Hierarchical linear models tested intervention, time, and interactions as fixed effects with participant as random effects. RESULTS: Patients whose caregivers received PEPRR did not differ on FACT-BMT between baseline and 6 months (mean = +3.74; 95% CI, -3.54 to 11.02) compared with patients of caregivers in eTAU (mean = +3.16; 95% CI, -2.88 to 9.20) even though CG-distress was decreased by PEPRR (mean = -0.23; 95% CI, -0.448 to -0.010) compared with those receiving eTAU (mean = +0.27; 95% CI, 0.033-0.504) at 6 months. CONCLUSIONS: PEPRR reduced CG-distress without affecting their patient's FACT-BMT score. The FACT-BMT may not have distinguished unique psychological changes associated with their caregiver receiving PEPRR.