We aimed to investigate whether increased levels of FXIII and/or a low prevalence of the protective Leu allele (of the Val34Leu FXIII polymorphism) occur in relatives of patients with severe CAD. 185 healthy male relatives aged 65 or less were recruited from 125 patients with multi-vessel CAD and compared to 185 healthy, age-matched controls. The relatives and controls were similar in terms of clinical parameters. FXIII B-subunit levels were elevated in relatives, 1.11 microg/mL (1.08-1.14), compared with controls, 1.00 microg/mL (0.97-1.04), P <0.0001 but FXIII A2B2 levels did not differ between the groups. There was a strong correlation between FXIII B-subunit and the insulin resistance syndrome, however, adjusted B-subunit levels remained significantly higher in relatives. There was no difference in genotype frequency at the FXIII Val34Leu polymorphism between relatives and controls. FXIII B-subunit levels are elevated in the relatives of CAD patients and this is independent of other cardiovascular risk factors.