Healthy postmenopausal women and hypertensive patients show an imbalance in the modulation of autonomic nervous control of the cardiovascular system, which may increase the cardiovascular risk. OBJECTIVE: To examine the heart rate variability (HRV) response to estrogen replacement therapy (ERT) and its association with changes in metabolic variables in hypertensive postmenopausal women. METHODS: A double-blind, placebo-controlled clinical trial was conducted in 30 hypertensive postmenopausal women receiving 180 mg/day of verapamil. The experimental group (n=16) received 0.625 mg OD of natural conjugated estrogens during 4 months, while control group (n=14) received a placebo. Lipids, lipoproteins, apolipoproteins, glucose and insulin were measured at 0, 2 and 4 months. HRV was determined in time and frequency domains using a 24-h Holter before and after ERT. RESULTS: Significant higher values of spectral and non-spectral parameters of HRV, associated with a lower LF/HF ratio, were found at the end of 4 months of ERT. Multiple regression analysis revealed that estrogen treatment itself and changes in total cholesterol, LDL-cholesterol, glucose and waist circumference, contributed to the changes observed in indexes reflecting parasympathetic activity in time and frequency domains. CONCLUSIONS: We conclude that ERT partially improves HRV favoring increased parasympathetic drive, and that part of the effect may be mediated by changes in metabolic variables.