BACKGROUND Electrophysiological properties of the atrial endocardium compared to epicardium are not well understood. The purpose of this study was to compare the electrophysiological properties and vulnerability to arrhythmia induction from these regions. RESULTS Transseptal endocardial and percutaneous epicardial mapping were performed in a porcine model (n = 7). Two opposing 4-mm electrophysiological catheters were positioned endocardially and epicardially. A circular mapping catheter (CMC) was positioned at the ostium of the common inferior pulmonary vein (CIPV) recording left atrial (LA)-PV potentials. Endocardial and epicardial effective refractory periods (ERPs) at two basic cycle lengths (CLs) of 600 and 400 ms were recorded from four anatomic locations (CIPV, LA appendage, right superior PV, and LA posterior wall). Atrial repetitive response (ARR) induction was also tested from endocardial and epicardial sites. Overall, 254 ERP measurements (mean 36.3 per animal) and 84 induction attempts (mean 12 per animal) were performed. The ERP was significantly shorter in the epicardium compared to the endocardium at basic CL of 400 ms (P = 0.006) but not at CL of 600 ms (P = 0.2). In addition, only the epicardium demonstrated ERP shortening when the CL of the basic drive was shortened (P = 0.03). ARR could be induced more often from the epicardium (P = 0.002) and fibrillatory activity with epicardial/endocardial dissociation was recorded (n = 3). Also, the earliest PV activation site on the CMC was noted to be different in 16.5% of cases during epicardial and endocardial pacing. CONCLUSIONS The electrophysiological characteristics of the atrial epicardium are different from the endocardium with a shorter ERP and more frequent ARR induction by programed stimulation.