Raised factor VIII coagulant activity has been associated with Ischaemic Heart Disease and Myocardial Infarction (MI). We measured FVIII:C and FVIII:Ag levels in 288 white European patients characterised for extent of atheroma by coronary angiography and for a history of MI by WHO criteria, and 313 white European healthy controls. FVIII:Ag levels were higher in patients than controls after adjustment for confounding variables (1.17 IU/ml patients, 1.03 IU/ml controls [p <0.0005]), whereas FVIII:C levels were lower in patients (1.26 IU/ml patients, 1.45 IU/ml controls [p<0.0005]). FVIII:Ag levels were higher in patients with MI and with angiographic evidence of atheroma than controls. FVIII:Ag levels but not FVIII:C levels were a significant independent risk factor for MI in multivariate analysis (Odds Ratio 2.40[1.35-4.27] [p = 0.003]). No association of FVIII:Ag or FVIII:C levels and presence or extent of atheroma was found in multivariate analysis. In conclusion, this study found an independent association of FVIII:Ag but not FVIII:C with MI.