Prespecified thresholds of quantitatively assessed pupillary light reflex < 4% and the Neurological Pupil index ≤ 2 predict unfavorable neurological outcomes with zero-percent false-positive rate in comatose out-of-hospital cardiac arrest survivors. Combined with neuron-specific enolase, pupillometry thresholds offer a robust multimodal neuroprognostication strategy, especially relevant for centers facing challenges in obtaining neurophysiological data.