BACKGROUND AND PURPOSE: Autonomic dysfunction is associated with worse outcome of ischemic stroke patients by mechanisms that are not fully understood. There is evidence of autonomic influence in cerebrovascular control but this has not been studied in acute stroke. Therefore, we examined the relationship between heart rate variability (HRV) and baroreflex sensitivity (BRS) in dynamic cerebral autoregulation in the early hours post ischemia, and its impact in clinical and radiological outcome. METHODS: We prospectively enrolled 26 patients with acute ischemic stroke in middle cerebral artery. Arterial blood pressure (Finometer), cerebral blood flow velocity (transcranial Doppler), and electrocardiogram were recorded within 6 h. HRV was assessed by the standard side deviations of normal inter-beat intervals, spectral analysis and non-linear entropy indexes. Spontaneous BRS was assessed by spectral and sequence methods. Dynamic cerebral autoregulation was assessed by transfer function analysis (coherence, phase and gain). Infarct volume was calculated from computed tomography at 24 h. Clinical outcome was assessed by the modified Rankin scale. RESULTS: Increased BRS and HRV high frequencies power, both reflecting increased vagal modulation, were correlated with higher gain values of cerebral autoregulation (p < 0.05). The higher vagal modulation was also associated with later large infarct volumes (p < 0.05) but not with clinical outcome. CONCLUSIONS: Increased vagal modulation in early hours of acute ischemic stroke, may interfere with cerebrovascular control and is associated with larger infarcts. Understanding the mechanisms that govern this complex interplay can be useful as novel therapeutic targets to improvement of outcome.