The present study was designed to investigate the protective effects of calcitonin gene-related peptide (CGRP) in a porcine model of cardiopulmonary resuscitation (CPR). Twelve pigs were anesthetized, paralyzed, mechanically ventilated with oxygen, and were monitored for electrocardiograph (ECG), arterial pressure, right atrial pressure, airway pressure. Ventricular fibrillation (VF) was induced in all animals by the application of 30 V of alternating current (60 Hz) across the heart, and remained untreated for 3 min, followed by conventional CPR with pneumatic piston device (Thumper) for 15 min. At 18 min of VF a single dose of vasopressin was given, and followed by defibrillation attempts. Two groups were studied. Group 1: Six pigs were used as saline control. Group 2: 0.3 nmol/kg CGRP was given 15 min prior to induction of VF. All animals in the CGRP pretreated group achieved a return of spontaneous circulation (ROSC) and survived more than 2 h (100%), whereas none of the saline control animals achieved ROSC. Blood gases were not significantly different between the groups. However, CGRP group had significantly higher arterial blood pressure and coronary perfusion pressure than control group during CPR. Pretreatment with CGRP affords a cardioprotective effect in this model of whole body ischemia.