OBJECTIVE Stroke is a major cause of long-term disability and morbidity worldwide. C-reactive protein (CRP), an inflammatory marker, has been reported to be an independent predictor of functional outcome after ischemic stroke (IS). Because several single nucleotide polymorphisms (SNPs) at the CRP locus have been linked with elevated CRP levels, we hypothesized that CRP genetic variation might be associated with functional disability in patients after first-ever IS. METHODS A total of 1716 patients from western China with first-ever IS were genotyped for the CRP SNPs rs1130864 and rs1800947 using the ligation detection reaction method. Functional outcome was assessed 3 months after IS using the modified Rankin Scale. Then, we tested the association of CRP SNP genotypes with stroke outcome after adjusting for non-genetic factors. RESULTS Our data showed a significant association between the T allele of rs1130864 and poor functional outcome in IS patients. In addition, the presence of TT+CT genotypes of rs1130864 strongly predicted functional disability within the first 3 months, even after adjusting for potential confounders. CONCLUSIONS Our study indicates that SNP rs1130864 in the CRP gene is an independent predictor of 3-month functional outcome in patients with first-onset IS in a Han Chinese population. Further studies in different ethnic groups are needed to validate our findings.