Background: Many survivors of cardiovascular arrest remain in a postanoxic coma. The neurologist’s task is to provide the most accurate assessment of the patient’s neurologic prognosis through a multimodal approach of clinical and technical tests. The aim of this study is to analyze differences and developments in the concept of neurological prognosis assessment and in-hospital outcome of patients over a five year-period. Methods: This retrospective observational study included 227 patients with postanoxic coma treated in the medical intensive care unit of the University Hospital, Mannheim from January 2016 to May 2021. We retrospectively analyzed patient characteristics, post-cardiac arrest care, and the use of clinical and technical tests for neurological prognosis assessment and patient outcome. Results: Over the observation period, 215 patients received a completed neurological prognosis assessment. Regarding the multimodal prognostic assessment, patients with poor prognosis (54%) received significantly fewer diagnostic modalities than patients with very likely poor (20.5%), indeterminate (24.2%), or good prognosis (1.4%;p= 0.001). The update of the DGN guidelines in 2017 had no effect on the number of performed prognostic parameters per patient. The finding of bilaterally absent pupillary light reflexes or severe anoxic injury on CT contributed most to a poor prognosis category (OR 8.38, 95%CI 4.01–7.51 and 12.93, 95%CI 5.55–30.13, respectively), whereas a malignant EEG pattern and NSE > 90 µg/L at 72 h resulted in the lowest OR (5.11, 95%CI 2.32–11.25, and 5.89, 95%CI 3.14–11.06, respectively) for a poor prognosis category. Assessment of baseline NSE significantly increased over the years (OR 1.76, 95%CI 1.4–2.22,p< 0.001), and assessment of follow-up NSE at 72 h trended to increase (OR 1.19, 95%CI 0.99–1.43,p= 0.06). In-hospital mortality was high (82.8%), remained unchanged over the observation period, and corresponded to the number of patients in whom life-sustaining measures were discontinued. Conclusions: Among comatose survivors of cardiac arrest, the prognosis remains poor. Prognostication of a poor outcome led nearly exclusively to withdrawal of care. Prognostic modalities varied considerably with regard to their contribution to a poor prognosis category. Increasing enforcement of a standardized prognosis assessment and standardized evaluation of diagnostic modalities are needed to avoid false–positive prognostication of poor outcomes.