The American Heart Association (AHA) currently recommends two-finger (TF) chest compression for infants. A previous study demonstrated that two-thumb (TT) with lateral chest wall compression provided significantly higher arterial pressures than did the TF method. Limitations of that study included the lack of an asphyxial model and non-standardized compression forces. To test the hypothesis that TT chest compression generates higher arterial pressures than does the TF method, using an asphyxial model. Also, by standardizing sternal compression force (SCF), the authors sought to show that the increased pressures are the result of thoracic compression. The study was a randomized, crossover trial in immature swine weighing 10 kg. Each swine was sedated, anesthetized, paralyzed, intubated, and mechanically ventilated on room air. A femoral arterial catheter was placed. Cardiac arrest was induced by asphyxiation and verified by ECG and pressure tracings. Eleven AHA-certified basic rescuers each randomly performed four 1-minute trials of external chest compressions. Each of the two CPR techniques was performed, with and without feedback of SCF. Compression forces were measured using the Uniforce Sensor System (Force Imaging Technology, Inc., Chicago, IL). During the feedback mode, the rescuers were instructed to maintain sternal pressures at 20-25 psi. During the nonfeedback mode, the rescuers were blinded to the force transducer. All compressions were analyzed for systolic blood pressure (SBP), diastolic blood pressure (DBP), and SCF. Data were analyzed using repeated-measures analysis of variance (RMANOVA) and Tukey multiple comparisons (alpha = 0.05). A total of 2,297 compressions were analyzed. The TT method produced significantly higher SBPs both with (25% increase) and without (57% increase) feedback when compared with the TF. The DBPs were not significantly different. The SCFs were also significantly higher in the two groups with feedback. The SCFs in the TF groups did not reach the standardized value of 20 psi, whereas in the TT groups, both were in the range of 20-25 psi. The TT method produced significantly higher SBPs. The authors were unable to demonstrate that the increased SBPs were secondary to the thoracic compression component because the rescuers did not reach the predetermined SCF in the TF groups. In this swine model of infant CPR, TT chest compression is an easier and more effective method.