We describe a process for assisting seriously ill patients and their caregivers in prioritizing their preferences for care during advanced illness. Thirty-two seriously ill patients and their caregivers participated in seven 90-minute focus groups conducted cross-sectionally in Denver, Colorado; San Francisco, California; and Washington State. Fourteen expert-defined end-of-life quality indicators were presented to each group, and quantitative unweighted rankings were obtained through patient and caregiver preferences. Aggregated weightings were used to rank the top five quality measures for exploration of open-ended questions. Pain management was the most important quality indicator among all three groups. Overlap in preferences were found for at least two of the groups for symptom management, monitoring medical issues, advance care preferences and assessment of family and caregiver involvement. Caregivers were more focused on bereavement support. Variation in preferences for end-of-life care by patients and their caregivers reflects the need to understand the individual decision-making regarding end-of-life care. Quality improvement activities are beginning to address these needs.