The importance and function of serum uric acid (UA) levels in patients with cardiovascular disease or stroke are unclear. We sought to evaluate the appropriate UA levels for stroke patients and the association between endogenous UA levels and clinical outcomes in acute ischemic stroke (AIS) patients, particularly regarding the possible interaction between gender and UA levels with respect to AIS prognosis. We examined 303 patients who had an onset of ischemic stroke within 48 h. Of those, 101 patients received thrombolytic treatment. Serum UA (mu mol/L) levels were measured the second morning after admission. Patient prognosis was evaluated 90 days after clinical onset by modified Rankin Scale. Patients were divided into four groups according to serum UA quartiles. A binary multivariate logistic regression model was used to assess clinical relevance in regard to functional outcome and endogenous UA levels. Analysis of subgroups by gender and normal glomerular filtration rate were also been done. Poor functional outcome was associated with older age, history of atrial fibrillation, or higher baseline National Institutes of Health Stroke Scale scores. After adjustment for potential confounders, patients with higher UA levels (> 380 mu mol/L) or lower UA levels (a parts per thousand currency sign250 mu mol/L) were 2-3 times more likely to have a poor outcome (OR 2.95, 95 % CI 1.14-7.61; OR 2.78, 95 % CI 1.02-7.58, respectively) compared to the baseline group (UA level 316-380 mu mol/L). The same results were observed in thrombolyzed patients. Patients with high and low UA levels were 9-18 times more likely to having poor outcomes compared to the baseline group (UA level: 316-380 mu mol/L; OR 18.50, 95 % CI: 2.041-167.67; OR 9.66, 95 % CI 1.42-65.88, respectively). In men, patients with high UA levels were 6 times more likely to have poor outcomes compared to the baseline group (UA level: 279-334 mu mol/L; OR 6.10, 95 % CI 1.62-22.93). However, female patients with UA level 271-337 mu mol/L were seven times more likely to perform badly compared to the baseline group (UA level > 337 mu mol/L, OR 7.06, 95 % CI 1.00-49.81). Serum UA levels in an appropriate range were associated with better outcome in patients with AIS but may be harmful when too high or too low. The association of UA levels with AIS prognosis differed in male and female patients, which highlights the necessity of stratifying by gender in investigations of cerebrovascular risk factors.