AIMS: Activation of angiotensin II receptor type 1 (AT(1)) has been shown to mediate the structural and electrical remodelling of the atrial myocardium associated with atrial fibrillation. We hypothesized that AT(1) genotypic variation is associated with atrial fibrillation or diseases predisposing to atrial fibrillation such as hypertension, heart failure, ischemic heart disease, and myocardial infarction in the general population. METHODS: We re-sequenced the AT(1) gene in 760 individuals with atrial fibrillation and identified 2 non-synonymous variants (I103T and A244S) which were subsequently genotyped in the prospective Copenhagen City Heart Study (n=10,603) and the prospective Copenhagen General Population Study (n=60,647). RESULTS: Risk of atrial fibrillation for heterozygotes for AT(1) genetic variants A244S and I103T/A244S versus non-carriers was increased by 2.7 (1.5-5.1) and 2.6 fold (95% CI: 1.6-4.2) for men. CONCLUSIONS: Heterozygosity for the non-synonymous AT(1) genetic variants A244S and I103T/A244S associated with increased risk of atrial fibrillation in men. The AT(1) might be a target for the pharmaceutical industry. This finding needs to be validated in independent studies.