Because closed chest cardiopulmonary resuscitation (CCCPR) achieve restoration of spontaneous circulation (ROSC) in less than 50% of cases, and because of the apparent physiological superiority of open-chest cardiopulmonary resuscitation (OCCPR), we evaluated OCCPR in out-of hospital cardiac arrest in cases who did not respond to standard external cardiopulmonary resuscitation with advanced life support. Over a period of 12 years, OCCPR was performed in 33 patients with out-of-hospital cardiac arrest arising from different causes, after unsuccessful attempts to achieve ROSC with CCCPR efforts over 7-121 min (median 25 min). With OCCPR, ROSC was achieved in 13/33 patients. Of these, two recovered to discharge (one with no neurological deficit and one with mild brain damage). The other 11 rearrested either in the emergency department after a median period of 70 min of resuscitation, or in the intensive care unit after a median period of 104 h. One case of iatrogenic cardiac injury was observed. The OCCPR attempts were well accepted by the public. Our data suggest that OCCPR is more effective than CCCPR in achieving ROSC outside hospital in patients with major cardiac disease and prolonged arrest. OCCPR is feasible in the out-of-hospital setting. Survival without neurological deficit cannot be expected when CCCPR with no-flow is continued beyond 25 min.