BACKGROUND To reduce the risk of adjustment problems associated with hematopoietic stem cell transplant (HSCT) for adolescents/young adults (AYAs), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: 1) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; 2) decrease risk factors of illness-related distress and defensive coping; and 3) increase outcomes of self-transcendence and resilience. METHODS This was a multisite randomized, controlled trial (COG-ANUR0631) conducted at 8 Children's Oncology Group sites involving 113 AYAs aged 11-24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase's Resilience in Illness Model (RIM). Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning, and resilience at baseline (T1), postintervention (T2), and 100 days posttransplant (T3). RESULTS At T2, the TMV group reported significantly better courageous coping (Effect Size [ES], 0.505; P =.030). At T3, the TMV group reported significantly better social integration (ES, 0.543; P =.028) and family environment (ES, 0.663; P =.008), as well as moderate nonsignificant effect sizes for spiritual perspective (ES, 0.450; P =.071) and self-transcendence (ES, 0.424; P =.088). CONCLUSIONS The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high-risk cancer treatment. We recommend the TMV be examined in a broader population of AYAs with high-risk cancers. Cancer 2014;120:909-917. © 2013 American Cancer Society. Adolescents/young adults undergoing stem cell transplant for cancer who received a therapeutic music video intervention demonstrated significant posttransplant improvement in resilience-related outcomes of courageous coping, family support/communication, and social support from friends and health care providers.