OBJECTIVES: The recommended epinephrine administration interval during CPR is between 3 and 5 min. However, the optimal interval for improving cerebral perfusion remains controversial. This study aimed to evaluate the effects of epinephrine administration interval of 3 min or 5 min on cerebral perfusion pressure (CEPP) and cortical cerebral blood flow (CCBF) in a porcine cardiac arrest model. METHODS: An experimental model of ventricular fibrillation (VF) cardiac arrest was conducted using 26 pigs, randomised into 3-min and 5-min interval groups. Six minutes after VF induction, all pigs received 4 min of chest compressions, followed by 20 min of advanced cardiovascular life support, including defibrillation and intravenous epinephrine administration. CEPP and CCBF were measured simultaneously throughout the experiment. RESULTS: Each of the experimental groups comprised 13 pigs. The 3-min group showed higher CEPP compared with the 5-min group in between 16 min and 20 min, 26 min and 30 min from VF induction: mean (95 % Confidence intervals) 26.8 (4.7-49.0) mmHg for 3-min group and 11.3 (-5.7-28.3) mmHg for 5-min group in 18 to 20 min from VF induction, which showed biggest difference. No significant difference was observed in CCBF between the 3-min and 5-min groups throughout the resuscitation phase (from the first epinephrine administration): The relative ratios 6 to 8 min after VF induction ranged from 0.21 to 0.86 in the 3-min group, and 0.35 to 0.77 in the 5-min group. CONCLUSION: The 3-min epinephrine administration interval showed a higher CEPP compared with the 5-min interval. No significant differences were found in the CCBF between the two interval groups.