Objective: To evaluate the efficacy of a simple and novel cardiopulmonary resuscitation (CPR) technique, nasopharyngeal oxygen with intermittent nose-close and abdomen-compression (NPO2-NC-AC) in an animal model. Design: Prospective piglet study. Setting: In an animal physiology laboratory of a medical university. Piglets: Six healthy piglets <14 days old. Interventions: Spontaneous breathing of the anesthetized piglets (n = 6) was medically ceased until severe bradycardia (<20 beat/min). NPO2-NC-AC CPR trial was then initiated by delivering NPO2 at 1.0–1.5 L/kg/min and intermittently performing the NC-AC maneuver: (1) NC for inspiration, occluded nostrils for 1 sec; and (2) AC for expiration, released nostrils, and compressed the abdomen for 1 sec. NC-AC was repeated at a rate of 30/min for 5 min. This CPR trial was repeated three times in each piglet. Cardiopulmonary variables were monitored, recorded, and compared. Measurements and Main Results: A total of 18 CPR trials were performed. All of these acute life-threatening asphyxia events rapidly improved within 1 min of CPR. Cardiopulmonary variables recovered to the baseline levels and oxygenation continually increased. The intratracheal pressure (Ptr) values of positive end expiratory pressure and peak inspiratory pressure values were 4.3 ± 0.8 cmH2O and 26.2 ± 4.1 cmH2O, respectively. Chest wall movement was observed when the Ptr reached 17.5 ± 3.1 cmH2O. All six piglets fully recovered after 63.8 ± 7.2 min of experiment without additional support. Conclusions: NPO2-NC-AC is a simple and effective CPR technique for severe acute cardiopulmonary asphyxia in piglets. It may be clinically applicable for supportive or rescue use.