The aim was to investigate clinical characteristics of increased brachial pulse pressure (PP) during long-term follow-up (23 years) as a marker of arterial stiffness in 9704 healthy subjects. The association of baseline variables with an increasing PP burden during the study period was analysed by univariate analysis. In addition, the association between different biological variables at baseline and increasing PP at follow-up, as well as the cross-sectional association with PP at follow-up, were examined by multiple regression analysis. The prospective analysis showed in men that the following baseline variables predicted (p<0.05) increased PP at follow-up: age, fasting glucose, triglycerides, heart rate, smoking, family history of hypertension and cholesterol. Among women, the same predictors were established (p<0.05), except for smoking and triglycerides, but in addition body mass index (BMI). The cross-sectional analysis obtained at the last survey, showed that the following variables (p<0.05) were associated with increased PP in men: fasting glucose, age, BMI, cholesterol and family history of hypertension. In females, similar findings were noted (p<0.05), but in addition there was a negative correlation with smoking. In conclusion, several well-known cardiovascular risk factors, such as glucose, BMI, heart rate, family history of hypertension and cholesterol in particular, are long-term predictors of increased PP in both genders.