The role of uric acid (UA) in the process of atherothrombosis is controversial. Although serum UA has powerful antioxidant properties, epidemiological studies showed that UA was a risk factor for cardiovascular diseases and was positively associated with proinflammatory markers. Relations between baseline UA and changes in UA circulating levels with C-reactive protein (CRP) and interleukin-6 (IL-6) after 3 years of follow-up in a cohort of 892 Italian men and women aged 21 to 98 years was investigated. Subjects had complete baseline and follow-up data for UA, inflammatory markers, and covariates. An autoregressive approach was used to study such a relation. In adjusted analyses, baseline UA and changes in UA predicted a 3-year change in CRP (p = 0.028), but not IL-6 (p = 0.101). The relation between UA and CRP persisted after adjustment for baseline IL-6. Subjects with high UA at baseline had a progressively higher probability of developing clinically relevant increased IL-6 (>2.5 pg/ml) and CRP (>3 mg/L) during 3 years. In conclusion, our study suggests that in a population-based cohort, baseline UA and changes in circulating UA during 3 years of follow-up predict changes in circulating CRP independent of relevant confounders, including baseline IL-6.