Background/Objectives: To compare the prognostic and therapeutic management, as well as the neurological outcomes, of comatose patients following out-of-hospital cardiac arrest(OHCA) across two distinct time-periods, reflecting advances in post-cardiac arrest(CA) care and neuro-logical prognostication. Methods: a retrospective, single-centre study at Careggi University Hos-pital in Florence, Italy. We compared the prognostic-therapeutic management and neurological outcomes of all comatose adult patients (aged ≥18years) admitted to the Emergency Depart-ment(ED) following OHCA between 1 June 2018 and 31 May 2020 with those admitted between 1 January 2024 and 31 December 2025. Neurological outcome was assessed using the Glas-gow-Pittsburgh-Cerebral-Performance-Category(CPC) scale. CPC scores of 1–2 were classified as favourable outcomes, whereas scores of 3–5 were considered poor outcomes. Results: A total of 121 and 122 patients were included in the 2018–2020 and 2024–2025 cohorts, respectively. Using the 2014-ERC/ESICM guidelines, 59/121 patients(48.7%) were correctly identified. In the 2024–2025 cohort, the 2025-ERC/ESICM guidelines correctly identified 106/122 patients(86.8%)(46/62 with poor and 60/60 with favourable outcomes). Neurophysiological prognostication was per-formed earlier in this cohort than in the 2018–2020 cohort. Applying the 2025 guidelines to the 2018–2020 cohort increased the number of patients with correctly predicted outcomes to 93/121(76.8%). Conclusions: Implementation of the 2025-ERC/ESICM guidelines improved the accuracy and timeliness of neurological prognostication after OHCA. The more recent cohort un-derwent prognostication that focused on identifying both poor and good outcomes, based on a greater number of complementary predictors, which potentially increased reliability. Accurate neurological prognostication is particularly important in patients with poor outcomes, who were more frequently managed with withdrawal of life-sustaining treatment.