BACKGROUND AND OBJECTIVES: Epinephrine has been the mainstay drug of choice for cardiac resuscitation for more than 30 years. Its vasopressor effects favoring initial resuscitation point to its beta-adrenergic action. However, its beta-adrenergic actions may have detrimental effects. The aim of the present experimental study was to evaluate the efficiency of coadministration of Esmolol, an ultra-short-acting beta-blocker, and of epinephrine in a swine model of cardiac arrest. MATERIALS AND METHODS: Fourteen pigs (19 +/- 2 Kg) were anesthetized and instrumented. Ventricular Fibrillation (VF) was produced electrically. After induction of VF, the animals were left untreated for 5 minutes. Animals were randomized into two groups, control and study group. Six animals were used in the control group, and 8 in the study group. The control group received 10 ml of normal saline via a peripheral vein, while the study group received 0.4 mg/kg Esmolol in 10 ml dilution. Epinephrine was administered to all animals after the first unsuccessful defibrillation set, and all animals received standardized Advanced Life Support. RESULTS: Seven animals (87.5%) restored cardiac rhythm compatible with a pulse in the Esmolol group, compared to 2 animals (33.3%) in the control group (p = 0.018). The average time until restoration of circulation was 16 +/- 3.2 minutes in our control group and 12.8 +/- 1.4 minutes in Esmolol group (p = 0.059). Coronary perfusion pressure (CPP) was significantly higher in the Esmolol group. CONCLUSIONS: Esmolol improves significantly the outcome of cardiopulmonary resuscitation and the average time of restoration of circulation, while in the proposed dosage does not alter the CPP at the beginning of CPR. However, it augments CPP from the sixth minute of CPR and afterwards.