European Resuscitation Council Vasopressin during Cardiopulmonary Resuscitation Study was a prospective, randomized, double blind, controlled trial carried out in 33 centers to evaluate efficacy of vasopressin in the setting of out-of-hospital cardiac arrest. The study consisted of 1186 adult patients who had an out-of-hospital cardiac arrest and presented with resistant ventricular fibrillation (three attempts of defibrillation had failed), n= 472; pulseless electrical activity, n= 186; or asystole, n= 528. After undergoing randomization patients received either 1 mg of epinephrine (n= 589) or 40 IU of vasopressin (n=597) intravenously, followed by 20 ml of normal saline. If spontaneous circulation was not restored within 3 minutes, the same drug at the same dose was repeated. If spontaneous circulation was still not restored, the patients were allowed additional injections of epinephrine at the discretion of emergency physician managing the CPR attempt. Additional administration of sodium bicarbonate, atropine, lidocaine, amiodarone and fibrinolysis was also permitted. The primary end point of the study was survival to hospital admission, whereas secondary end point was survival to hospital discharge. The baseline characteristics were similar in both the groups. Mean age was 66 years, more than two-thirds were male, only 18% received bystander CPR and time to institution of basic life support was nearly 8 min, and the first defibrillation attempt was carried out after a mean of 7 min from the basic life support. The first injection of study drug was given after a mean of 10 min. The rate of survival to hospital admission was higher among patients with witnessed cardiac arrest than among those with an unwitnessed cardiac arrest (38.3% v. 16.1%, p< 0.001), and those who received basic life support within 10 minutes as compared to those receiving support after 10 min (43.8% v. 20.7%, p< 0.001). There was no difference in occurrence of primary end point with either of the study drugs in patients with ventricular fibrillation or pulseless electrical activity. However, in patients with asystole more patients were likely to survive to hospital admission if they received vasopressin than if they were treated with epinephrine as the initial therapy (29% v. 20.3%, p=0.02). Vasopressin group also had better hospital discharge rates (4.7% v. 1.5%, p=0.04). Even in patients, in whom spontaneous circulation was not restored with two injections of the study drug and therefore required additional treatment with epinephrine, survival to hospital admission (25.7% v. 16.4%, p= 0.002) and hospital discharge (6.2% v. 1.7%, p= 0.002) was significantly superior in vasopressin group compared to epinephrine group, although neurological improvement was similar in the two groups. Thus, in the treatment of refractory cardiac arrest, vasopressin followed by epinephrine may be more effective.