Arterial stiffness is an independent predictor of cardiovascular events in a hypertensive population. Serum levels of matrix metalloproteinase (MMP)-9 are associated with arterial stiffness and predict cardiovascular risk. We investigated the role of MMP-9 polymorphism -1562C>T on blood pressure (BP) and arterial stiffness in a newly diagnosed hypertensive population. Untreated hypertensive patients (n=215, mean age 46+/-13 years) were studied. Supine BP, carotid-femoral pulse wave velocity (PWV) and augmentation index were assessed. Serum biochemistry and plasma MMP-9 concentrations were measured and genotyping performed following extraction of genomic DNA. BP, aortic PWV and serum MMP-9 levels were significantly higher in T-allele carriers of the -1562C>T polymorphism with a significant gene-dose effect (P<0.0001). In a stepwise regression model adjusting for known or likely determinants, the 1562C>T polymorphism emerged as an independent predictor of systolic BP (R(2)=0.25, P<0.0001), diastolic BP (R(2)=0.16, P<0.0001) and PWV (R(2)=0.47,P<0.0001). This is the first study to show the effect of MMP-9 polymorphism on BP and aortic stiffness in a hypertensive population. These results suggest that hypertensive patients carrying the T allele may be at increased risk of cardiovascular events.