Several studies have found that uric acid (UA) level is associated with an increased risk for hypertension, but the association could be confounded by metabolic factors that were not included in these previous studies. UA level and risk for incident hypertension was examined prospectively among men who participated in the Health Professionals' Follow-up Study. From among men without hypertension at the time blood was collected, 750 participants who developed hypertension during the subsequent 8 yr and 750 age-matched controls were selected. In addition to adjustment for standard hypertension risk factors and renal function, adjustments controlled for fasting insulin, triglyceride, and cholesterol levels. The mean age of participants was 61 yr, and mean plasma UA level was 6.0 mg/dl (SD 1.25 mg/dl). The multivariable relative risk (RR) for a 1-SD increase in UA was 1.02 (95% confidence interval [CI]0.87 to 1.18); the RR comparing the highest with lowest quartile of UA was 1.08 (95% CI 0.71 to 1.63). The multivariable RR associated with a 1-SD increase in UA was 1.38 (95% CI 1.05 to 1.81) for men aged <60 yr and 0.90 (95% CI 0.74 to 1.10) for men >or=60 yr (P = 0.04 for interaction). However, further adjustment for fasting insulin, triglyceride, and cholesterol levels attenuated the results (RR for men <60 yr 1.24; 95% CI 0.93 to 1.66). In conclusion, no independent association between UA level and risk for incident hypertension was found among older men.