BACKGROUND: It remains unclear which is more effective to increase survival after out-of-hospital cardiac arrest in those with public-access defibrillation, bystander-initiated chest compression-only cardiopulmonary resuscitation (CPR) or conventional CPR with rescue breathing. METHODS AND RESULTS: A nationwide, prospective, population-based observational study covering the whole population of Japan and involving consecutive out-of-hospital cardiac arrest patients with resuscitation attempts has been conducted since 2005. We enrolled all out-of-hospital cardiac arrests of presumed cardiac origin that were witnessed and received shocks with public-access automated external defibrillation (AEDs) by bystanders from January 1, 2005, to December 31, 2009. The main outcome measure was neurologically favorable 1-month survival. We compared outcomes by type of bystander-initiated CPR (chest compression-only CPR and conventional CPR with compressions and rescue breathing). Multivariable logistic regression was used to assess the relationship between the type of CPR and a better neurological outcome. During the 5 years, 1376 bystander-witnessed out-of-hospital cardiac arrests of cardiac origin in individuals who received CPR and shocks with public-access AEDs by bystanders were registered. Among them, 506 (36.8%) received chest compression-only CPR and 870 (63.2%) received conventional CPR. The chest compression-only CPR group (40.7%, 206 of 506) had a significantly higher rate of 1-month survival with favorable neurological outcome than the conventional CPR group (32.9%, 286 of 870; adjusted odds ratio, 1.33; 95% confidence interval, 1.03-1.70). CONCLUSIONS: Compression-only CPR is more effective than conventional CPR for patients in whom out-of-hospital cardiac arrest is witnessed and shocked with public-access defibrillation. Compression-only CPR is the most likely scenario in which lay rescuers can witness a sudden collapse and use public-access AEDs. © 2012 American Heart Association, Inc.