Background: Many studies have shown that autonomic activation is one of the major factors in the etiology of hypertension. Furthermore, sympathovagal imbalance may be responsible for arrhythmias and sudden cardiac death. The aim of the present study was to compare and to evaluate the effects of short-term therapy with amlodipine and verapamil on heart rate variability (HRV) in patients with essential hypertension. Methods: Forty patients with essential hypertension (11 men and 29 women, mean age 50.5+/-10.4 years) were included in the study. Patients with cardiac, metabolic, or any other systemic disease were excluded. Patients were randomized to receive either amlodipine (10 mg; n=20) or verapamil (240 mg; n=20). Patients underwent 24-h Holter monitoring assessment before treatment and after the 4-week treatment period. Standard deviation of normal RR intervals (SDNN), standard deviation of all 5-min mean normal RR intervals (SDANN), square root of the mean of the sum of the squares of differences between adjacent RR intervals (r-MSSD), and pNN50 (time domain variables) and TF, high-frequency power (HF), low-frequency power (LF), and sympathovagal balance (LF/HF; frequency domain variables) were analyzed before and after treatment. Results: Blood pressure (BP) was reduced to a similar degree, from 182/104 to 128/85 mmHg with verapamil and from 174/100 to 124/86 mmHg with amlodipine (verapamil p<0.001; amlodipine p<0.001). This study revealed that amlodipine had no significant effect on any of the time or frequency domain parameters. In contrast, in patients on verapamil, there were significant increases in all time domain parameters, and the LF/HF ratio was significantly decreased (p<0.05). Conclusions: These results suggest that verapamil may have additional positive effects on sympathico-parasympathetic control beyond lowering blood pressure compared with amlodipine, even after short-term treatment in hypertensive patients.