The relationship between serum uric acid (UA) and outcomes after acute ischemic stroke remains debatable in human studies, and the sex effect on this association has yet to be explored. Here, we investigated these associations in a prospective study from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline UA levels were measured in 3284 acute ischemic stroke patients. Primary outcome was defined as a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months. UA levels were significantly higher in men than women (310.6 ± 96.1 vs 257.5 ± 89.9 μmol/L, P < 0.001). The association between serum UA and the primary outcome was appreciably modified by sex (P-interaction = 0.007). After multivariate adjustment, a high serum UA was associated with a decreased risk of primary outcome in men [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.44-0.91; P-trend = 0.01] but not in women (OR, 1.29; 95% CI, 0.83-2.01; P-trend = 0.15), when two extreme quartiles were compared. Subgroup and sensitivity analyses further confirmed these sex-specific findings. Our study indicated that there was a sex-specific association between serum UA and prognosis of acute ischemic stroke. Elevated serum UA was positively associated with better prognosis in men, but not in women.