To evaluate the effects of permanent vagal stimulation on cardiovascular system, 10 patients, affected by drug-resistant epilepsy with no primitive cardiovascular pathologies, were assessed prior to VNS surgery. A complete echocardiographic study [conventional and tissue Doppler imaging (TDI)], 24-h blood pressure (BP) monitoring and HRV evaluation were performed. The above mentioned parameters were investigated without any substantial changes to drug treatment during a check-up subsequent to VNS activation [mean: 7.7 months]. The results obtained show that while the anthropometrical data and both conventional and TDI echocardiography were unvaried compared to baseline, BP showed a significant increase of both systodiastolic values. Moreover, a close scrutiny of the most affected period of the BP increase (zenith between 16:31 and 17:30 pm) (systolic BP 114.7 mmHg vs 95.3 mmHg, P < 0.0001; diastolic BP 70.9 mmHg vs 56.9 mmHg, P < 0.001) showed a significant increase of the high frequencies components (HF) (28.4 +/- 2.7 vs 36 +/- 5.3, P < 0.05) and a significant reduction in low frequency/HF ratio (2.3 +/- 0.3 vs 1.7 +/- 0.3, P < 0.0001). The present study confirms the intrinsic cardiovascular safety and reliability of VNS procedures on both BP and HF and LF profiles and suggests that a primitive VNS-mediated central impingement on vagal efferents, independently by the antiepileptic mechanism, correlated to an moderate increase of parasympathetic activity, which in turn might play a protective role in seizure-triggered alterations of cardiovascular dynamic.