Both cardiac autonomic dysfunction adn cardiovascular risk factors are related to and excess risk of mortality. We sought to determine whether the major cardiovascular risk factors are associated with diminished heart rate variability (HRV), prolonged QTc interval, or increased QT dispersion (QTD). Male (n = 1030) and female (n = 957) subjects, aged 55-74 years, who participated in the population-based MONICA Augsburg survey 1989/90 were assessed for the presence of cardiovascular risk factors such as diabetes, hypertension, obesity, dyslipidemia, smoking, and low physical activity. Lowest quartiles for time domain indexes of HRV (SD of R-R intervals [SDNN], max-min difference), QTc > 440 ms, and QTD > 60 ms determined from 12-lead resting ECG were used as cutpoints. In men, after adjustment for age and alcohol consumption, significant independent determinants for the lowest quartiles of SDNN were diabetes, obesity, and smoking. Independent contributors to prolonged QTc were hypertension, obesity, smoking, and low physical activity, whereas for increased QTD it was only hypertension. In women, diabetes was the only contributor to low SDNN, and hypertension was the only determinant of prolonged QTc. In conclusion, diabetes is the primary determinant of reduced HRV in the general population, while hypertension is the primary contributor to prolonged QTc in both sexes. However, obesity and smoking contribute to autonomic dysfunction in men but not women. Thus, a selectivity and sex-related differences exist among the various cardiovascular risk factors as to their influence on autonomic dysfunction.