Objectives/HypothesisTo investigate the association between epistaxis and atherosclerotic cardiovascular disease.Study DesignCase‐control cohort study.MethodsThis study included patients from the tertiary‐care ear, nose, and throat department at the University Hospital of Zurich between December 1, 2016 and June 1, 2017. We assessed the cardiovascular risk profiles in a group of 41 patients presenting with epistaxis, and a group of 41 matched controls, focusing on a surrogate parameter for atherosclerosis: the carotid intima‐media thickness (CIMT).ResultsWith a mean of 1.06 mm (standard deviation [SD] = 0.17), CIMT values were on average 26% higher in epistaxis patients than in their controls, with a mean of 0.84 mm (SD = 0.14; P < .001). Occurrence of severe epistaxis was also associated with lower ankle–brachial index values at 0.96 (SD = 0.12) versus 1.05 (SD = 0.17) (P < .001) and significantly higher QRISK2 relative risks (an algorithm for predicting cardiovascular risk) than found in the control group (1.81, SD = 0.97 vs. 1.35, SD = 0.28; P = .028). A binary logistic regression model, adjusted for possible confounders, showed an odds ratio of 2.5 for the occurrence of epistaxis per increase in CIMT of 0.1 mm in the study population (95% confidence interval: 1.56‐4.11; P < .001).ConclusionsThe occurrence of severe epistaxis was shown to be closely associated with the prevalence of atherosclerotic cardiovascular disease. Accordingly, patients affected by epistaxis should be regarded as at an elevated cardiovascular risk, which indicates the need for appropriate further medical assessment and preventive measures.Level of Evidence3bTrial registrationClinical trials NCT03092973 Laryngoscope, 129:783–787, 2019