Background Uric acid levels are increased in patients with kidney dysfunction. We tested the hypothesis that uric acid may be associated with kidney disease progression. Study Design Cohort study. Setting & Participants 5,808 participants of the Cardiovascular Health Study. Predictor Uric acid levels. Outcomes & Measurements Kidney disease progression was defined as a decrease in estimated glomerular filtration rate (GFR) of 3 mL/min/1.73 m2 per year or greater (≥0.05 mL/s) and as incident chronic kidney disease (CKD). Measures of kidney function were estimated GFR using the Modification of Diet in Renal Disease Study equation. Results Higher quintiles of uric acid levels were associated with greater prevalences of estimated GFR less than 60 mL/min/1.73 m2 (<1.00 mL/s) of 7%, 14%, 12%, 25%, and 42% for quintiles 1 (≤4.41 mg/dL ≤262 μmol/L), 2 (4.41 to 5.20 mg/dL 262 to 309 μmol/L), 3 (5.21 to 5.90 mg/dL 310 to 351 μmol/L), 4 (5.91 to 6.90 mg/dL 352 to 410 μmol/L), and 5 (>6.90 mg/dL >410 μmol/L), respectively. In comparison, there was only a modest, but significant, association between quintiles of uric acid levels and progression of kidney function decrease, with adjusted odds ratios of 1.0, 0.88 (95% confidence interval CI, 0.64 to 1.21), 1.23 (95% CI, 0.87 to 1.75), 1.47 (95% CI, 1.04 to 2.07), and 1.49 (95% CI, 1.00 to 2.22) for quintiles 1 through 5, respectively. No significant association was found between uric acid level and incident CKD (adjusted odds ratio, 1.00; 95% CI, 0.89 to 1.14). Limitations Measurements of albuminuria were not available. Conclusions Uric acid levels are associated strongly with prevalent CKD. In comparison, greater uric acid levels had a significant, but much weaker, association with progression of kidney disease.