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Background-Transnasal evaporative cooling has sufficient heat transfer capacity for effective intra-arrest cooling and improves survival in swine. The aim of this study was to determine the safety, feasibility, and cooling efficacy of prehospital transnasal cooling in humans and to explore its effects on neurologically intact survival to hospital discharge. Methods and Results-Witnessed cardiac arrest patients with a treatment interval Յ20 minutes were randomized to intra-arrest cooling with a RhinoChill device (treatment group, nϭ96) versus standard care (control group, nϭ104). The final analysis included 93 versus 101 patients, respectively. Both groups were cooled after hospital arrival. The patients had similar demographics, initial rhythms, rates of bystander cardiopulmonary resuscitation, and intervals to cardiopulmonary resuscitation and arrival of advanced life support personnel. Eighteen device-related adverse events (1 periorbital emphysema, 3 epistaxis, 1 perioral bleed, and 13 nasal discolorations) were reported. Time to target temperature of 34°C was shorter in the treatment group for both tympanic (102 versus 282 minutes, Pϭ0.03) and core (155 versus 284 minutes, Pϭ0.13) temperature. There were no significant differences in rates of return of spontaneous circulation between the groups (38% in treated subjects versus 43% in control subjects, Pϭ0.48), in overall survival of those admitted alive (44% versus 31%, respectively, Pϭ0.26), or in neurologically intact survival to discharge (Pittsburgh cerebral performance category scale 1 to 2, 34% versus 21%, Pϭ0.21), although the study was not adequately powered to detect changes in these outcomes. Conclusions-Prehospital