There are limited data on the influence of genetic polymorphisms in atrial fibrillation (AF) stroke risk. We hypothesized that a functional haemostatic polymorphism, that is, the factor VII -323 Del/Ins polymorphism, would influence the prothrombotic state associated with AF, as well as stroke risk. Other functional polymorphisms were also tested. METHODS: We performed a cross-sectional study of 119 AF patients, who were compared to 96 patients with stroke secondary to AF. In the first patient group, we analysed plasma prothrombin fragment 1+2 levels (F1+2, an index of thrombin generation) to reflect the prothrombotic state of AF. RESULTS: AF patients carrying the -323 Ins allele had lower plasma F1+2 levels (P=0.015). After multivariate analysis adjusted by age, sex and clinical risk factors, advanced age and 807C/T polymorphism of glycoprotein Ia (GPIa) gene were associated with higher risk of ischaemic stroke (OR: 1.06; P=0.003 and OR: 1.91; P=0.025), whilst FVII Ins -323 allele was associated with lower stroke risk (OR: 0.41; P=0.017). CONCLUSION: FVII -323 Ins allele may modulate the prothrombotic state associated with AF. Despite the small sample size, we found that FVII Ins -323 allele could be associated with a lower stroke risk in AF, whereas the 807C/T polymorphism may increase the risk.