The + 1444 C > T variant of C-active protein (CRP) may be associated with inflammatory markers and influence the development of atherosclerosis. We investigated the relationship between CRP + 1444 C > T polymorphism, inflammatory markers and the extent of cerebral atherosclerosis. CRP and fibrinogen were measured within 24h of hospital admission in 349 ischemic stroke (IS) or transient ischemic attack (TIA) patients who had cerebral large-artery stenoses. The number of stenoses closest to the 50th percentile of the series was used to divide the study patients into two groups: lower and greater extent groups. Only in 222 smokers, the distribution in the recessive model (CC versus CT + TT) was significantly different between lower and greater extent groups (P = 0.007), and CC genotype was independently associated with a greater extent of atherosclerosis (odds ratio, 3.41; 95% CI, 1.124 - 10.347; P = 0. 030). Genotype didn't influence inflammatory markers, except for fibrinogen in smokers. The coexistence of the CC genotype and higher fibrinogen led to a greater extent of cerebral atherosclerosis in smokers. These findings suggests that CRP + 1444 C > TCC genotype is an independent genetic marker of the greater extent of cerebral atherosclerosis, and in conjunction with higher fibrinogen, increases the extent of cerebral atherosclerosis in smokers from IS patients.