Large artery mechanical properties are a major determinant of pulse pressure and cardiovascular outcome. Sex differences in these properties may underlie the variation in cardiovascular risk profile between men and women, in relation to age. To investigate sex differences in the age-related stiffening of large arteries. Cross-sectional. One hundred and twenty healthy men and women were recruited and divided equally into tertiles by age: young (mean ± SD, 23 ± 5 years), middle-age (47 ± 3 years) and older (62 ± 7 years). Lipids, mean arterial pressure and heart rate were matched within each tertile. Carotid tonometry and Doppler velocimetry were used to measure indices of large artery stiffness. There was no sex difference in systemic arterial compliance (SAC) in the young group (mean ± SEM, 0.61 ± 0.05 arbitrary compliance units (ACU) in women compared with 0.67 ± 0.04 ACU in men), but in the older population women had lower SAC than men (0.27 ± 0.03 ACU compared with 0.57 ± 0.04 ACU respectively;P < 0.001). Measures independent of aortic geometry (distensibility index and aortic impedance) indicated that stiffness was lower in young women than in men (P < 0.05), but the reverse was true in the older population (P < 0.01). This paralleled the brachial and carotid pulse pressures, which were lower in young (P < 0.01) and higher in older women compared with those in men (P < 0.05). Follicle stimulating hormone concentrations correlated strongly (r values 0.39–0.65) with all indices of central, but not peripheral, arterial function, whereas concentrations of luteinizing hormone, progesterone and oestradiol correlated less strongly. In men and women matched for mean pressures, the age-related stiffening of large arteries is more pronounced in women, which is consistent with changes in female hormonal status.