Introduction Prognosis in patients suffering out-of-hospital cardiac arrest is poor. Higher survival rates have been observed only in patients with ventricular fibrillation who were fortunate enough to have basic and advanced life support initiated soon after cardiac arrest. An ability to predict cardiac arrest outcomes would be useful for resuscitation. Changes in expired end-tidal carbon dioxide levels during cardiopulmonary resuscitation (CPR) may be a useful, noninvasive predictor of successful resuscitation and survival from cardiac arrest, and could help in determining when to cease CPR efforts. Methods This is a prospective, observational study of 737 cases of out-of-hospital cardiac arrest. The patients were intubated and measurements of end-tidal carbon dioxide taken. Data according to the Utstein criteria, demographic information, medical data, and partial pressure of end-tidal carbon dioxide (Pet CO 2 ) values were collected for each patient in cardiac arrest by the emergency physician. We hypothesized that an end-tidal carbon dioxide level of 1.9 kPa (14.3 mmHg) or more after 20 minutes of standard advanced cardiac life support would predict restoration of spontaneous circulation (ROSC). Results Pet CO 2 after 20 minutes of advanced life support averaged 0.92 ± 0.29 kPa (6.9 ± 2.2 mmHg) in patients who did not have ROSC and 4.36 ± 1.11 kPa (32.8 ± 9.1 mmHg) in those who did ( P < 0.001). End-tidal carbon dioxide values of 1.9 kPa (14.3 mmHg) or less discriminated between the 402 patients with ROSC and 335 patients without. When a 20-minute end-tidal carbon dioxide value of 1.9 kPa (14.3 mmHg) or less was used as a screening test to predict ROSC, the sensitivity, specificity, positive predictive value, and negative predictive value were all 100%. Conclusions End-tidal carbon dioxide levels of more than 1.9 kPa (14.3 mmHg) after 20 minutes may be used to predict ROSC with accuracy. End-tidal carbon dioxide levels should be monitored during CPR and considered a useful prognostic value for determining the outcome of resuscitative efforts and when to cease CPR in the field.