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To evaluate the effect of no assisted ventilation cardiopulmonary resuscitation on neurologically intact survival compared with ten positive pressure ventilations/minute cardiopulmonary resuscitation in a pig model of cardiac arrest.Prospective randomized animal study.Animal laboratory.Sixteen female intubated pigs (25.2 ± 2.1 kg) anesthetized with propofol.fter 8 mins of untreated ventricular fibrillation, the intubated animals were randomized to 8 mins of continuous chest compressions (100/min) and either no assisted ventilation (n = 9) or 10 positive pressure ventilations/min (Smart Resuscitator Bag with 100% O2 flow at 10 L/min) (n = 7). The primary end point, neurologically intact 24-hr survival, was evaluated using a pig cerebral performance category score by a veterinarian blinded to the cardiopulmonary resuscitation method.During cardiopulmonary resuscitation, aortic and coronary perfusion pressure were similar between groups but cerebral perfusion pressure was significantly higher in the positive pressure ventilation group (33 ± 15 vs. 14 ± 14, p = .04). After 7.5 mins of cardiopulmonary resuscitation, arterial pO2 (mm Hg) and mixed venous O2 saturation (%) were significantly higher in the positive pressure ventilation compared with the no assisted ventilation group (117 ± 29 and 41 ± 21 vs. 40 ± 24 and 10.8 ± 7; p = .01 for both). Paco2 was significantly lower in the positive pressure ventilation group (48 ± 10 vs. 77 ± 26, p = .01). After 24 hrs, four of nine no assisted ventilation pigs were alive with a mean cerebral performance category score of 3 ± 0 vs. five of seven alive and neurologically intact positive pressure ventilation pigs with a cerebral performance category score of 1 ± 0.3 (p < .001 for cerebral performance category score).No assisted ventilation cardiopulmonary resuscitation results in profound hypoxemia, respiratory acidosis, and significantly worse 24-hr neurologic outcomes compared with positive pressure ventilation cardiopulmonary resuscitation in pigs.