The positive effect of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy is considered to be mediated by the afferent pathways of the vagus nerve, but the efferent pathways may influence the cardiac autonomic activity. AIM OF THE STUDY: To assess the effects of VNS on cardiac autonomic modulation in epilepsy patients, over three months of neurostimulation. CLINICAL RATIONALE FOR THE STUDY: Linear and non-linear heart rate variability (HRV) analysis can provide information on the sympathovagal balance and reveal particularities of the central control of the autonomic cardiovascular function. MATERIALS AND METHODS: Using Biopac Acquisition System, we analysed HRV parameters in resting condition and during sympathetic and parasympathetic activation tests in five patients with drug-resistant epilepsy, who underwent VNS procedure. RESULTS: During the sympathetic and vagal activation tests, all five patients presented normal responses of cardiac autonomic activity, reflected in RMSSD, HFnu and LF/HF dynamics in both HRV evaluations. No bradycardia, cardiac arrhythmia or orthostatic hypotension was registered during the two evaluations. CONCLUSIONS: Our results indicate that VNS appears not to alter the cardiac autonomic function after three months of neurostimulation. HRV analysis is a useful tool for evaluating cardiac autonomic modulation in epilepsy patients during VNS therapy. CLINICAL IMPLICATIONS: Patients with decreased HRV should be periodically monitored. Cardiac changes in patients with epilepsy are important because of the additional risk of arrhythmias mediated through the autonomic dysfunction.