Several factors, including metabolic profile, are predictive of response to standard antiviral therapy in patients with chronic hepatitis C. In a retrospective study, it was investigated whether uric acid, involved in metabolic syndrome, could be included. A total of 153 patients (56.2% males; mean age 45.7 +/- 11.3 years) treated with pegylated-interferon and ribavirin were included. Eighty-five were infected with hepatitis C virus (HCV) genotype 1 or 4 and 68 with genotype 2 or 3. Viral load was >1,000,000 IU/ml in 101, < or =1,000,000 IU/ml in 35 and unknown in 17 patients. Ishak fibrosis score was < or =4 in 81, >4 in 15 and unknown in 57 patients. Mean serum uric acid was 5.05 +/- 1.3 mg/dl. Sustained virological response (negative serum HCV-RNA 6 months after treatment cessation) was achieved in 102 patients (67%). In the final logistic model, serum uric acid level > or =5.8 mg/dl (OR = 0.46; 95% CI: 0.30-0.62), viral load (OR = 0.29; 95% CI: 0.09-0.92) and HCV genotype (OR = 0.23; 95% CI: 0.09-0.60) were identified as the most important factors independently influencing clinical outcome. The prognostic role of serum uric acid was confirmed on the sub-sample reporting Ishak fibrosis score (OR = 0.49; 95% CI: 0.28-0.85). Serum uric acid level > or =5.8 mg/dl is predictive of poor response to HCV treatment. Prospective studies are needed to clarify the issue.