The main cause of increased mortality in end-stage renal disease (ESRD) is cardiovascular disease (CVD). Complement factor H (CFH) may affect risk of CVD. Our study investigates a role of CFH Y402H polymorphism as a potential risk factor of CVD in a large group of patients. A group of 1200 patients with ESRD and 818 healthy controls were genotyped for the Y402H (T1277C) polymorphism. There was a significant difference in genotype frequencies between patients with CVD and those without CVD and healthy controls (p<0.001). Homozygosity for the C allele in CVD patients was associated with an odds ratio of 7.28 (95 % CI 5.32-9.95). No significant difference was found between patients without CVD and controls. Multivariate logistic regression analysis showed that Y402H genotype was independently associated with cardiovascular comorbidity in ESRD patients. This is the first study suggesting an association between CFH gene polymorphism and susceptibility to CVD in dialyzed patients.