To assess the feasibility and predictive ability of regional cerebral oxygen saturation monitoring during cardiopulmonary resuscitation by emergency medical technicians. Methods: This prospective observational study included 33 cardiac arrest patients who received cardiopulmonary resuscitation in a prehospital setting. Patients were connected to a near-infrared spectrometer through two disposable probes immediately after entering the ambulance. The monitor, which showed regional cerebral oxygen saturation readings, was obscured by covering it with a sheet of paper. Regional cerebral oxygen saturation was measured continuously until hospital arrival. Outcome variables included the prehospital return of spontaneous circulation, survival to hospital admission, and survival at 90 days. Results: For patients who survived >90 days after hospital admission (n = 2), the mean regional cerebral oxygen saturation values upon ambulance and hospital arrival were 24% and 60%, respectively; for patients who did not survive (n = 31), the mean regional cerebral oxygen saturation values were 15% and 17%, respectively. Regional cerebral oxygen saturation values increased to a greater extent between ambulance arrival and hospital arrival in patients who survived >90 days (median, 36%; interquartile range, 32-40%) than in those who did not survive (0; 0-6%; P = 0.07). Additionally, regional cerebral oxygen saturation values were not related to the prehospital return of spontaneous circulation or survival to hospital admission. Conclusion: Regional cerebral oxygen saturation could be monitored during resuscitation by emergency medical technicians, and it can be used during physiological monitor-guided cardiopulmonary resuscitation.