OBJECTIVE: The objectives were to assess the feasibility of using a novel, comprehensive chaplain-led spiritual life review interview to develop a personal Spiritual Legacy Document (SLD) for persons with brain tumors and other neurodegenerative diseases and to describe spiritual well-being (SWB), spiritual coping, and quality of life (QOL) of patients and their support persons (SP) before and after receipt of the SLD. METHODS: Patient-SP pairs were enrolled over a 2-year period. Assessments included the Functional Assessment of Chronic Illness Therapy-Spiritual Expanded Version, Brief Religious Coping Scale, Brief COPE Inventory, and QOL Linear Analog Scale. Baseline assessments were completed prior to an audio-recorded spiritual life review interview with a chaplain. RESULTS: Thirty-two patient/SP pairs were enrolled; 27 completed baseline assessments and the interview. Twenty-four reviewed their SLD and were eligible for follow-up. A total of 15 patients and 12 SPs completed the 1-month follow-up; 10 patients and seven SPs completed the 3-month follow-up. Patients endorsed high levels of SWB and spiritual coping at baseline. Both patients and SPs evidenced improvement on several aspects of SWB, spiritual coping, and QOL at 1 month, but patients’ decreased financial well-being was also observed. Patients and SPs demonstrated favorable changes in peacefulness and positive religious coping at both time points. CONCLUSIONS: A chaplain-led spiritual life review is a feasible intervention for patients with neurodegenerative disease and results in beneficial effects on patients and SPs.