OBJECTIVES To investigate whether patients with primary open angle glaucoma (POAG) have a higher proportion of ischemic heart disease (IHD) development. DESIGN A population-based retrospective cohort study, using the National Health Insurance Database (NHID) from 1st January, 2001, to 31st December, 2011, in Taiwan. METHODS 3510 subjects with POAG were enrolled into the POAG group and 14040 subjects without glaucoma into the comparison group. The comparison group consisted of randomly selected individuals, matched with the POAG group based on age, gender, and index date (date of enrollment) at a ratio of 1:4. The participants of both groups should have no IHD before the index date, and they were followed until the end of 2011 to see whether they had new-onset IHD or not. Kaplan-Meier curves were used to compare the cumulative incidence of IHD between the two groups. Frailty model, a specialized form of Cox regression analysis, was used to estimate the crude and adjusted hazard ratio (HR) of IHD. Analyses were adjusted by age, gender, and systemic comorbidities (i.e. diabetes, hypertension, hyperlipidemia, atrial fibrillation and congestive heart failure). RESULTS The mean age of the cohort was 57.6±11.0 years. There were slightly more males than females (51.6% vs. 48.4%). A log-rank test comparing Kaplan-Meier curves of the two groups revealed a significantly higher cumulative incidence of IHD in the POAG group (p-value<0.001). In the univariate analysis by Frailty model, POAG patients had a significantly higher hazard of IHD (unadjusted HR = 2.32; 95% confidence interval 1.93 to 2.79). After adjustment, results remained significant (adjusted HR = 1.41; 95% confidence interval 1.16 to 1.72). CONCLUSION People with POAG may suffer from IHD more often than those without glaucoma.