This study was performed to compare pericardiocentesis guided by a pacing current applied through the pericardiocentesis needle with the traditional method of monitoring ST segment elevation from the needle tip electrogram. ST segment elevation was measured at 3 mm from the epicardium, after epicardial contact, after epicardial penetration and again at 3 mm from the epicardium after epicardial penetration. Two millivolts of ST segment elevation gave the highest combined positive (86%) and negative (79%) predictive value for epicardial contact by the pericardiocentesis needle between the two groups with the largest difference: 3 mm from the epicardium before contact and after epicardial penetration. Therefore, ST segment monitoring cannot reliably determine the point of epicardial contact. To determine the optimal stimulus strength for pulse generator-guided pericardiocentesis, pacing studies were performed using 2, 4, 6, 8 and 10 mA unipolar stimulus strengths. The pacing studies were performed both with and without a hemodynamically significant pericardial effusion to determine if increased pericardial pressure altered the pacing threshold. A 4 mA unipolar cathodal stimulus was chosen because it captured the ventricle only with direct contact of the epicardium. Ten dogs were instrumented and cardiac tamponade produced so that a subxiphoid approach to the epicardium with the pacing needle electrode could be attempted. During pericardiocentesis, needle tip electrograms were recorded, alternating with pacing attempts using a 4 mA unipolar stimulus. In all 10 dogs, the effusion was entered and epicardium was contacted as indicated by capture. No myocardial perforation or coronary artery or venous injuries were produced. These findings support the use of a pulse generator to guide pericardiocentesis.