Background Inflammation plays an important role in coronary artery disease (CAD). Complement Factor H (CFH) gene has been analyzed in relation to CAD in several studies with conflicting results. The aim of the present study was to investigate the association between the CFH Y402H polymorphism and CAD in Chinese. Methods and results About 336 patients were enrolled, included 166 patients with CAD and 170 controls. The SNP at CFH Y402H was genotyped by ligase detection reaction and plasma levels of CFH were assayed by enzyme-linked immunosorbent assay. Analysis of genotype frequencies did not reveal any significant difference between CAD patients and controls. There were significant differences in the frequencies of C allele and C allele carriers between early-onset CAD and controls. After adjustment of clinical parameters, significant association was identified for CFH Y402H polymorphism, with C allele carriers having a higher risk of early-onset CAD than carriers of TT genotype (odds ratio [OR] 4.66, 95% CI: 1.23-17.62, P=0.02). There was no difference of plasma CFH levels between CAD group and controls. Conclusions CFH Y402H polymorphism is associated with early-onset CAD in Chinese.