ABSTRACT: Serum uric acid (SUA) has long been associated with increased cardiovascular risk, with arterial stiffness proposed as a mediator. However, evidence on the association between SUA and arterial stiffness is limited to contradicting cross-sectional studies. In this analysis, we examined the longitudinal relationship between SUA and pulse wave velocity, a measure of arterial stiffness, in a community-dwelling population. We studied 446 women and 427 men participating in the BLSA (Baltimore Longitudinal Study of Aging), with 1409 and 1434 observations, respectively, over an average period of 6 years. At baseline, mean ages of women and men were 65±13 and 68±13 years; mean SUA, 4.6±1.1 and 5.7±1.3 mg/dL; mean pulse wave velocity, 8.1±1.7 and 8.6±1.9 m/s, respectively (P<0.0001). In gender-stratified models accounting for age, blood pressure, renal function, metabolic measures, and medications, there was a significant interaction between SUA and follow-up time in men (?=0.69; P=0.0002) but not in women. Men, but not women, in the highest gender-specific SUA tertile at baseline (SUA?6.2 mg/dL in men and SUA?4.9 mg/dL in women) had a greater rate of pulse wave velocity increase over time than those in the lowest tertiles (?=0.997; P=0.012). This gender difference was lost when the distribution of SUA in men and women was made comparable by excluding hyperuricemic men (SUA?6.2 mg/dL). In conclusion, higher SUA was associated with greater increase in pulse wave velocity in men but not women; this association was lost when men with SUA?6.2 mg/dL were not included, suggesting a threshold for SUA association with arterial stiffness, which is more frequently reached in men.