OBJECTIVE: Spirituality has been linked to improved adjustment and functioning in individuals with cancer; however, its effect on quality of life following hematopoietic stem cell transplantation (HSCT) has not been well-studied. This study investigated changes in spirituality in hematologic cancer patients recovering from HSCT and relationships between spirituality and dimensions of quality of life following HSCT. METHODS: Participants (N = 220) completed measures of two dimensions of spirituality(meaning/peace and religious faith), depression, anxiety, fatigue, pain, and physical and functional well-being prior to transplant and at 1-, 3-, 6-, and 12-months posttransplant. RESULTS: Meaning/peace declined at 1-month posttransplant and returned to pretransplant levels by 6-months posttransplant, and faith increased from pretransplant to 6-months posttransplant. Mixed-effects linear regression models indicated that greater pretransplant meaning/peace, but not religious faith, predicted less depression, anxiety, and fatigue, and better physical and functional well-being during the 12-months following transplant. CONCLUSIONS: The capacity to find meaning and peace may facilitate recovery followingHSCT. Results suggest that spirituality may be a resilience factor that could be targeted to improve quality of life for HSCT recipients.