BACKGROUND: Good outcomes for in-hospital cardiac arrest (IHCA) depend on a skilled resuscitation team, prompt initiation of high-quality cardiopulmonary resuscitation and defibrillation, and organisational structures to support IHCA response. We examined the role of nurses in resuscitation, contrasting higher versus lower performing hospitals in IHCA survival. METHODS: We conducted a descriptive qualitative study at nine hospitals in the American Heart Association's Get With The Guidelines-Resuscitation registry, purposefully sampling hospitals that varied in geography, academic status, and risk-standardised IHCA survival. We conducted 158 semistructured interviews with nurses, physicians, respiratory therapists, pharmacists, quality improvement staff, and administrators. Qualitative thematic text analysis followed by type-building text analysis identified distinct nursing roles in IHCA care and support for roles. RESULTS: Nurses played three major roles in IHCA response: bedside first responder, resuscitation team member, and clinical or administrative leader. We found distinctions between higher and lower performing hospitals in support for nurses. Higher performing hospitals emphasised training and competency of nurses at all levels; provided organisational flexibility and responsiveness with nursing roles; and empowered nurses to operate at a higher scope of clinical practice (eg, bedside defibrillation). Higher performing hospitals promoted nurses as leaders-administrators supporting nurses in resuscitation care at the institution, resuscitation team leaders during resuscitation and clinical champions for resuscitation care. Lower performing hospitals had more restrictive nurse roles with less emphasis on systematically identifying improvement needs. CONCLUSION: Hospitals that excelled in IHCA survival emphasised mentoring and empowering front-line nurses and ensured clinical competency and adequate nursing training for IHCA care. Though not proof of causation, nurses appear to be critical to effective IHCA response, and how to support their role to optimise outcomes warrants further investigation.