Objective: Hypotensive episodes are relatively frequent adverse effects during LDL apheresis. To evaluate the impact of LDL apheresis on autonomic cardiovascular control we investigated hypercholesterolemic patients before and after a single LDL apheresis in comparison to an age-matched control group. Methods: We continuously recorded systemic arterial blood pressure, electrocardiogram and respiration in 21 hypercholesterolemic patients (57 ± 15 years) on regular LDL apheresis treatment and 22 healthy control subjects (56 ± 4 years) during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex sensitivity and frequency spectra of R-R intervals and systolic blood pressure were evaluated by trigonometric regressive spectral analysis. Results: Hypercholesterolemic patients had reduced resting baroreflex sensitivity and high-frequency power of heart rate variability compared to controls. Consequently, there was a sympathetic predominance of heart rate modulation reflected by increased ratio of low-to-high frequency power of R-R intervals. Cardiovascular stimulation failed to adequately activate baroreflex mechanisms before LDL apheresis. After LDL apheresis, the parasympathetic response to cardiovascular stimulation improved and sympathetic outflow to peripheral vasculature was reduced. Baroreflex sensitivity remained low. Conclusion: Hypercholesterolemic patients on regular LDL apheresis treatment have significant autonomic dysfunction. A single LDL apheresis does not evoke sympathetic overactivation but improved deranged cardiovagal heart rate modulation in hypercholesterolemia.