Introduction: Cardiac arrest is a significant global health challenge, which leads to substantial morbidity and mortality, impacting 50 to 100 individuals per 100,000 in the general population. Ischemic heart disease is the primary cause, particularly in developed countries. Historically, survival rates following cardiac arrest with a good neurological outcome were low; however, advancements in emergency response, including early Cardio-Pulmonary Resuscitation (CPR), access to defibrillation, coronary revascularisation, intensive care and Targeted Temperature Management (TTM), have notably improved patient outcomes. The practice of TTM has evolved over the past two decades, advocating that Therapeutic Hypothermia (TH) enhances neurological outcomes; although there has been much controversy over optimal temperature ranges. Notwithstanding, international resuscitation guidelines continue to endorse TTM as a post-resuscitation neuroprotective strategy, recommending temperatures between 32° and 36° Celsius. To ensure patient comfort and prevent shivering during the administration of TTM, sedatives and neuromuscular blockers are administered, preventing an accurate neurological assessment. Despite the challenges of neurological prognostication post-cardiac arrest, current guidelines recommend a multimodal approach, including clinical examination, electrophysiological studies, biomarkers, and neuroimaging, to predict outcomes accurately. Aim: This research sought to develop and evaluate a protocol (Therapeutic Hypothermia and eArly Waking, THAW) for early waking of unconscious Out-of-Hospital-Cardiac-Arrest (OHCA) survivors for the purpose of performing a comprehensive neurological assessment. Methods: A mixed methods approach was used. In the development of the THAW protocol, qualitative data were obtained from a series of focus groups, which included the research team, the National Health Service Ethics committee, a clinical expert panel, OHCA survivors and their family members as well as the Essex Cardiothoracic Centre’s Clinical Governance Committee. Thematic analysis was undertaken to capture the varied perspectives and insights from the different stakeholder groups to inform the THAW protocol interventions. A prospective non-randomised sampling strategy was selected for the implementation of the THAW protocol and neurological indicators collected over a 72-hour period. Results: The THAW protocol assessed the safety and feasibility of an early waking protocol for unconscious survivors of OHCA treated with TTM at 33° Celsius, with a focus on the potential to reduce Intensive Care Unit (ICU) stay and mechanical ventilation duration through early neurological assessments. Despite an expected 50 percent mortality rate, largely due to neurological injuries, findings demonstrated that early waking and extubation with a mean mechanical ventilation duration of 21.4 hours, was feasible for 24 percent of patients, significantly reducing ICU length of stay without adverse events. Of these, seven patients (14%) were able to be transferred from the ICU to the cardiology High Dependency Unit (HDU) within the first 72 hours of their admission. The THAW protocol employed a combination of Intravenous Temperature Management (IVTM) and a counter-shivering strategy to manage core temperature, alongside physiological assessments and standard neurological exams like the Glasgow Coma Scale (GCS) and the Full Outline of UnResponsiveness (FOUR) score. Notably, the neuro biomarker and neurophysiological tests performed as part of the THAW protocol interventions, were not used to inform clinical decision-making, instead to be used in post hoc analysis to maintain objectivity. Conclusion: The THAW protocol demonstrated the safety and feasibility of an early waking protocol in OHCA survivors undergoing TTM at 33° Celsius. Highlighting the potential to expedite neurological prognostication and reduce ICU length of stay and mechanical ventilation duration. Through careful patient selection, the implementation of IVTM with a counter-shivering strategy, early neurological assessments can be integrated into critical care practices without adverse effects on patients.