Climacteric complaints are the main indication for hormone replacement therapy (HRT) in the clinical practice. Observational studies demonstrating a protective effect of HRT on cardiovascular disease (CVD) were conducted in early menopausal, young, symptomatic women. Vasomotor symptoms correlate with lower level of plasma antioxidant activity, an increased cardiovascular reactivity to stressful situations, elevated cholesterol, higher sympathetic nerve activity, impaired flow-mediated dilation, hypertension and a higher risk of aortic calcification. All the available findings indicate that hot flushes can be seen as a marker for underlying vascular changes among mid-life, otherwise healthy, climacteric women. Thus, young, healthy symptomatic postmenopausal women differ from those without vasomotor symptoms with regard to cardiovascular risk factors. Therefore, responses to HRT can change in terms of cardiovascular outcomes according to the baseline vasomotor complaints. This point may explain, at least in part, the negative/null effects of HRT on cardiovascular disease observed in the trials where HRT was given to largely asymptomatic, elderly women.