Abstract The purpose of the study was to evaluate the interests of electrophysiologic study (EPS) after infusion of isoproterenol in patients with syncope and negative EPS in control state. Methods 1350 patients were consecutively admitted for syncope and EPS. Patients were included if they had no history of tachycardia, a normal Holter monitoring, a negative EPS in control state. EPS was repeated after infusion of 2–4 μg/kg of isoproterenol. Results 256 patients, 35 with exercise-related syncope and 105 with heart disease (HD), were recruited. After isoproterenol, an arrhythmia was identified as the sign associated with syncope in 102 patients (40%): SVT in 32 patients, VT in 36 patients, infrahisian 2nd or 3rd degree AV block in three patients and vasovagal reaction in 31 patients. Arrhythmias were more frequent in patients with HD (50/105) than in those without HD (52/151) ( p < 0.05); SVT tended to be more frequent in patients without HD ( n = 23) than in those with HD ( n = 9) ( p < 0.1); VT was more frequent in patients with HD ( n = 26) than in those without HD ( n = 10) ( p < 0.001). There was no relationship between a positive isoproterenol testing and occurrence of syncope at exercise (19/35 vs 81/221) ( p < 0.1). Conclusion isoproterenol infusion increased the sensitivity of EPS in patients with syncope, related or not to exercise, and with negative study in control state, but principally in those with HD. However, SVT was diagnosed in patients without HD and EPS associated with isoproterenol infusion remained an important and rapid tool to establish this diagnosis.