ABSTRACT Current intensive care unit (ICU) care delivery for acute respiratory failure fails to meet the needs of patients near the end of life, their families, and their interprofessional ICU teams. Efforts to improve end-of-life ICU care have focused on communication between families and clinicians. Yet, poor end-of-life outcomes for patients, families, and ICU teams remain intractable, in part because of the system-level processes and norms that drive ICU care delivery. Time-limited trials have promise to disrupt system-level drivers of poor quality end-of-life care and establish processes of care delivery that better support patients, families, and ICU teams. A time- limited “trial” is an agreement among patients, their surrogate decision makers, and clinicians to attempt life- sustaining treatment for a predefined period and then re-evaluate its utility. This patient care model was proposed by palliative care experts to address prognostic uncertainty, and navigate competing desires simultaneously held by many patients—to extend life when possible and to avoid prolonged life-sustaining treatment if the chance of recovery is low. Time-limited trials have been described in the literature, endorsed by palliative and critical care professional societies, and are currently used in ICU practice. Yet, time-limited trials remain poorly formalized in practice with little evidence to guide ICU clinicians in how to conduct trials. The central objective of this study is to define the optimal care delivery processes of a time-limited trial in acute respiratory failure. This application responds to NHLBI’s Notice of Special Interest in Palliative Care (NOT-HL- 20-737), including the focus on models of ICU-based palliative care for acute respiratory failure and on how ICU structure and culture influence palliative care delivery. This project is a sequential mixed methods, prospective observational study in five ICUs where time-limited trials are currently used. In Aim 1, focused ethnography of 50 time-limited trials in patients with acute respiratory failure will be used to map current processes of time-limited trial care delivery for patients with acute respiratory failure. In Aim 2, a prospective, observational cohort study in 5,810 patients with acute respiratory failure will be used to elucidate the relationships between time-limited trial processes and end-of-life outcomes for patients, surrogates, and ICU teams. Aims 2a and 2b will test whether time-limited trial processes are associated with better end-of-life outcomes and Aim 2c will characterize mechanisms by which processes influence end-of-life outcomes. This work will transform time-limited trials from a promising model into a clearly defined and optimized care delivery process. This process will be immediately actionable to guide frontline ICU teams currently using or considering time-limited trials. This study will also establish the necessary foundation for the design and testing of complex h...