Allergy is a systemic inflammatory disease that could theoretically affect the risk of cardiovascular disease (CVD) and diabetes through inflammatory pathways or mast cell-induced coronary spasm. Whether allergy is associated with an increased risk of CVD and diabetes is largely unknown. We investigated the association between atopy as assessed by IgE sensitization, a well-accepted biomarker of allergy, and incidence of ischemic heart disease, stroke, and diabetes in five Danish population-based cohorts. A total of 14,849 participants were included in the study. Atopy was defined as serum-specific IgE positivity to inhalant allergens. The Danish National Diabetes Register enabled identification of incident diabetes. Likewise, the Danish Registry of Causes of Death and the Danish National Patient Register provided information on fatal and non-fatal ischemic heart disease and stroke. Data were analyzed by Cox regression analyses with age as underlying time axis and adjusted for study cohort, gender, education, body mass index, alcohol intake, smoking habits, physical activity during leisure time, serum lipids, and blood pressure. The prevalence of atopy was 26.9 % (n = 3,994). There were 1,170, 817, and 1,063 incident cases of ischemic heart disease, stroke, and diabetes, respectively (median follow-up 11.2 years). The hazard ratios, HRs (95 % confidence intervals, CIs) for atopics versus non-atopics: for ischemic heart disease (HR 1.00, 95 % CI 0.86, 1.16), stroke (HR 1.18, 95 % CI 0.99, 1.41), and diabetes (HR 1.06, 95 % CI 0.91, 1.23). Our results did not support the hypothesis that atopy is associated with higher risk of ischemic heart disease, stroke, or diabetes. However, a small-moderately increased risk cannot be excluded from our data.