Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VU[. The association of serum-triglycerides with factor VII may differ between the genotypes, but the results of earlier studies were inconsistent and did not include older people. We studied FVII, triglycerides and the R/Q353 polymorphism in the Rotterdam Study. In 1158 older subjects (489 men and 669 women) FVII:C, factor VII:Chr, serum-triglycerides and the R/Q353-genotype were determined. In women triglycerides were positively associated with FVII:Chr and FVII:C (FVII:Chr: β = 12.4% PP/mmol/L, CI: 10.3-14.5; FVII:C: β = 13.1% PP/mmol/L, CI: 10.4-15.8). These associations varied by genotype (FVII:Chr:RR: β = 11.7, CI: 9.6-13.8, RQ/QQ: β = 7.9, CI: 4.6-11.2; FRII:C: RR: β = 12.5, CI: 9.5-15.5, RQ/QQ: β = 6.4, CI: In men, the associations of FVII:Chr and FVII:C with triglycerides were weaker (FVII:Chr: β = 5.9, CI: 4.1-7.7; FVII:C: β = 8.7, CI: 6.2-11.2). There was no difference between the genotype groups. These results suggest that only in older women the strength of the association of factor VII with serum-triglycerides varies according to genotype of the R/Q353 polymorphism.