The best method for employment of phased chest and abdominal compression-decompression (Lifestick) cardiopulmonary resuscitation (CPR) has yet to be determined. Of particular concern with using this technique is the combining of ventilation with the phased compressions and decompressions. Twenty domestic swine (50+/-1 kg) were equally divided into four groups. Following 10 min of untreated VF, CPR was begun. Group 1 received Lifestick (LS) CPR with only passive ventilation ('passive'); Group 2 received LS-CPR with synchronized positive pressure ventilations (ppv) at a chest compression ratio of 15:2 (15:2 S); Group 3 had LS-CPR with synchronized ppv at 5:1 (5:1 S); and Group 4 received LS-CPR with asynchronous ppv at 5:1 (5:1 A). Endpoints included hemodynamics, blood gases, minute ventilation, and 24 h outcome. Asynchronous ventilation (5:1 A) had significantly worse hemodynamics including aortic and right atrial systolic, aortic diastolic, and coronary perfusion pressures than the other groups (P<0.05). Passive ventilation had the poorest arterial and mixed venous blood gases (P<0.05), but did not differ from 15:2 S in minute ventilation produced (8 vs 10 l/min). No differences in outcome were seen. The ventilation technique combined with LS-CPR can make a significant difference in hemodynamics as well as ventilation. Optimizing other forms of basic and advanced cardiac life support through different ventilation methods deserves new consideration, including a re-examination of the current single rescuer recommendation of a 15:2 ratio. Optimal ventilation strategy when using the LS device at 60 compressions per min appears to be 5:1 S. Such data is important for conducting clinical trials with this new CPR adjunct.