Arterial stiffness is an independent indicator of cardiovascular risk. Autoantibodies (AAs) against angiotensin AT(1) receptor (AT(1)-AAs) and alpha(1)-adrenergic receptor ((alpha 1)-AAs) are important in the pathogenesis of hypertension. We identified the types of AT(1)-AAs and alpha(1)-AAs in normotensive subjects, with the aim of determining whether these antibodies predict aortic stiffness progression. Carotid-femoral pulse wave velocity (cf-PWV) was used to measure aortic stiffness. Overall, 816 subjects (71% of those invited) underwent a medical examination and evaluation of aortic stiffness. The types of AT(1)-AAs and alpha(1)-AAs were measured at baseline. Meanwhile, plasma renin, angiotensin 11(Ang II), and norepinephrine (NE) concentrations were measured at baseline and follow-up. Baseline mean cf-PWV was 9.90 +/- 0.84 m/s and follow-up was 10.51 +/- 1.12 m/s. The annualized Delta PWV was 0.12 +/- 0.08 m/s/year. At the end of follow-up, 129 normotensive subjects developed hypertension and 144 subjects had PWV progression. After adjustment for covariates, AA type was independently associated with Delta PWV, annualized Delta PWV, and abnormal PWV. In our study, the risk of developing hypertension (RR = 2.028, 95% CI: 1.227-3.351, P = 0.006) and PWV progression (RR = 2.910, 95% Cl: 1.612-5.253,P < 0.001) in AA-positive subjects was significantly higher than that in AA-negative subjects. Receiver operating characteristic (ROC) curve showed AA had an identify power to discriminate subjects with or without PWV and hypertension progression. We have shown for the first time that the types of A(1)-AAs and alpha(1)-AAs are independent predictors for aortic stiffness progression in normotensive subjects. Our data collectively support the utility of these AAs as potential markers of aortic stiffness.