Epidemiological studies have shown that a high serum uric acid concentration is a risk factor for coronary artery disease (CAD). However, the issue of whether it is an independent cardiovascular risk factor or simply a marker of co-existing conditions is a matter of controversy. In the present case-controlled study, we explored the association between serum uric acid and angiographically defined CAD in middle-aged subjects (356 CAD patients and 350 healthy individuals). Serum uric acid in CAD patients was significantly higher than that in healthy individuals (359 +/- 88.7 and 289 +/- 79.3 micromol/l, respectively, p < 0.01) and remained significantly higher after adjusting for confounding factors (F = 79.77, p < 0.01). The association between uric acid and CAD was not limited to the hyperuricemic range of values, but was also found in the high-normal range (p < 0.01). An unadjusted odds ratio (OR) of 5.0 was obtained in both genders (p < 0.01). Female patients with > 50% stenosis (clinically significant CAD), regardless of the number of diseased vessels, had higher uric acid concentrations than those with < 50% stenosis even after adjusting for confounders (F = 3.79, p = 0.01). In conclusion, we have demonstrated that high serum uric acid is independently associated with CAD and that uric acid determination could be useful as one of the markers of clinically significant CAD.