To examine and report burnout, secondary trauma, and compassion satisfaction in acute care nurse leaders through a large mixed-methods research study.Although nurse leaders are removed from daily patient care activities, the pervasive challenges in the work environment create conditions for professional burnout. Nurse leaders must garner compassion satisfaction from different sources, including peer and staff interactions.The Professional Quality of Life scale was given to nurse leaders at 29 hospitals in 1 health system. Sixteen leaders from 2 hospitals participated in qualitative interviews.Six hundred seventy-two nurse leaders from 29 hospitals reported similar levels of burnout across frontline, midlevel, and director-level leadership. Directors demonstrated higher levels of compassion satisfaction and lower levels of work-life balance. Four themes emerged representing areas of professional life that potentiate and alleviate compassion fatigue.All levels of nurse leaders must address the risk of burnout and can do so through individual and organizational resiliency strategies.