<p dir="ltr">Patients who are aware of their terminal cancer prognosis are more likely to receive end-of-life care consistent with their values. However, prognostic awareness has shown mixed associations with quality of life (QoL) outcomes. Based on theories of acceptance (i.e., Erikson’s stages of life development, Kubler-Ross’s stage model of grief, coping theories) and the Ottawa Decision Support Framework, acceptance of cancer may moderate relationships between prognostic awareness and QoL outcomes and end-of-life treatment preferences. Dyadic coping theories, such as the Systemic Transactional Model and the Dyadic Cancer Outcomes Framework, suggest that patients’ degree of prognostic awareness and acceptance of their illness may also impact their family caregivers’ QoL and end-of-life treatment preferences for the patient. The aim of the present study was to examine the potential moderating role of patient acceptance of cancer in the relationships between patient prognostic awareness and both patient and caregiver QoL and end-of-life treatment preferences. This study was a secondary analysis of cross-sectional data from advanced cancer patients (<i>n</i> = 243) and their caregivers (<i>n</i> = 87) enrolled in the multi-institutional Coping with Cancer-II study. Patient outcomes of physical, psychological, and existential QoL were examined in a moderation path analysis. Caregiver physical and psychological QoL were examined in separate moderation regressions. Patient and caregiver end-of-life treatment preferences were examined in multiple logistic regression moderation models. Results did not support my hypothesis, as patient illness acceptance did not moderate the relationships between patient prognostic awareness and patient and caregiver QoL outcomes and end-of-life treatment preferences. However, there were significant main effects of patient illness acceptance on their own physical, psychological, and existential QoL as well as caregiver psychological QoL. There were also significant main effects of patient prognostic awareness on their own physical QoL and both their own and their caregivers’ end-of-life treatment preferences. Findings suggest that increasing patient’s prognostic awareness and illness acceptance may help improve values-consistent end-of-life care and QoL outcomes in advanced cancer patient-caregiver dyads. Findings support timely conversations to promote advanced cancer patients’ prognostic awareness as well as further research examining the impact of acceptance-based interventions in advanced cancer.</p>