This prospective study evaluated the prognostic value of early neurobiochemical markers, neuron-specific enolase and astroglial protein S-100B, for long-term cognitive outcome after cardiac arrest. Six months after admission of a cohort of 80 consecutive patients, 26 survivors were able to undergo a neuropsychological test battery. Survivors showed low test performances in attention, learning/memory, and executive functioning. Neuropsychological bedside screening during the first month significantly differentiated between patients with and without long-term cognitive impairment. The neurobiochemical marker S-100B at day 3 after admission was found to predict significant proportions of variance in specific cognitive domains (learning/memory and executive functioning). The results indicate that early neuropsychological assessment might help identify patients who run at risk of long-term neuropsychological dysfunction. This study also suggests that especially the protein S-100B provides valuable information on long-term cognitive outcomes. To understand the exact relationship, results have to be replicated in larger trials. (JINS, 2009, 15, 344–353.)