The present prospective study evaluated the prognostic performance of serum neuron-specific enolase (NSE) measured at 24 and 72 hours after return of spontaneous circulation (ROSC) in a cohort of adult post-cardiac arrest patients treated without targeted temperature management (TTM). NSE was measured at 24 and 72 hours after ROSC in accordance with standardized clinical practice and guideline-supported prognostication time points. Here, ENO2 is linked to cardiac arrest.