Elevated serum uric acid (UA) levels strongly reflect and may even cause oxidative stress, insulin resistance, and metabolic syndrome, which are risk factors for the progression of liver disease. We sought to determine whether serum UA levels are associated with the development of cirrhosis or the presence of elevated serum liver enzymes. We used cohort data from the first National Health and Nutrition Examination Survey (NHANES I) to determine whether the baseline serum UA level was associated with the incidence of hospitalization or death due to cirrhosis among 5518 participants during a mean follow‐up of 12.9 years (range = 4‐21 years) after the exclusion of the first 4 years of follow‐up. We also used cross‐sectional data from NHANES 1988‐1994 (n = 10,993) and NHANES 1999‐2006 (n = 6186) to determine whether the serum UA level was associated with elevated serum alanine aminotransferase (ALT) or γ‐glutamyl transferase (GGT), two markers of hepatic necroinflammation. Compared to persons in the lower third of the distribution of serum UA (<4.8 mg/dL), those in the top third (>6 mg/dL) had a higher risk of cirrhosis‐related hospitalization or death [adjusted hazard ratio (AHR) = 2.8, 95% confidence interval (CI) =1.3‐5.7], whereas the risk was not substantially increased in persons within the middle third (serum UA level = 2.6‐4.8 mg/dL, AHR = 1.3, 95% CI = 0.6‐2.7). A higher serum UA level was associated with greater mean serum ALT and GGT levels and a greater probability of elevated serum ALT and GGT. Conclusion: The serum UA level is associated with the development of cirrhosis and the presence of elevated serum liver enzymes after adjustments for important causes and risk factors of chronic liver disease. (HEPATOLOGY 2010;)