Background: The presence of vascular disease (peripheral artery disease (PAD) and/or myocardial infarction (MI)) may impact on the risk of stroke and death among patients with incident AF. To test this hypothesis, we analyzed data from a large Danish prospective cohort, the Diet, Cancer and Health (DCH) study, to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease. Methods: Prospective cohort study of 57,053 persons (27,178 men and 29,876 women, respectively), aged between 50 and 64 years. The risk of vascular disease for stroke or death amongst 3,315 patients with incident AF (mean age 67.1 years; 2,130 male, 1,185 female) was assessed using Cox proportional hazard models, after a median followup of 4.8 years. Results: Of the subjects with AF, 417 (12.6%) had 'vascular disease' (PAD and/or prior MI). The risk of the primary endpoint (stroke or death) were significantly higher in patients with vascular disease at one year follow-up (crude hazard ratio (HR) 2.51 (1.91-3.29), with corresponding crude HRs for PAD and MI being 3.51 (2.40-5.13), and 1.99 (1.46-2.72), respectively. For the secondary endpoints of death or stroke individually, these risk estimates were similar (crude HR 2.48 (1.89-3.26) and 1.77 (1.18-2.66), respectively). After adjustment for risk factors within the CHADS(2) score, the adjusted HR for the primary endpoint (stroke or death) in patients with vascular disease was 1.91 (1.44-2.54), which was also significant for death (1.97(1.48-2.62)). Conclusion: Vascular disease (prior MI and PAD) is an independent risk factor for the primary endpoint of 'stroke or death' in patients with AF, even after adjustment for the CHADS(2) risk score, although this is driven by the impact on mortality. This reaffirms that patients with vascular disease represent a 'high risk' population which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis (that is, oral anticoagulation), which has been shown to significantly reduce the risk of stroke and death in AF.