Part of the international variation in the gender differences in total mortality remains unexplained. Although a continuous decrease in age-standardised death rates was observed in Italy, the difference between male and female rates became relatively small or even reversed (as the rate for ischaemic heart diseases). We performed an extensive evaluation of cardiovascular risk factors - demographic and clinical characteristics, biochemical parameters, and oxidative biomarkers - in a sample of healthy subjects (94 women and 75 men) from Central Italy and analysed their relationship with the response to ergometer exercise. In addition to a proportion of smokers similar to that observed in men, a clustering of peculiar female cardiovascular risk factors emerged. This included: higher platelet counts, low participation in leisure-time aerobic physical activities, hypertensive response to exercise (BMI-dependent, unlike in men), and low fraction of heart rate reserve. Physical inactivity and high serum IL-6 levels were independently predictive of having both chronotropic incompetence and abnormal heart rate recovery.