Background and Objectives: Patients suffer from the nitroglycerin (NTG)-induced headache, which is a major problem of nitrate therapy. We hypothesized that patients with nitroglycerin-induced headache had an underlying systemic vasomotion abnormality and there might be an increased nitroglycerin-mediated dilation (NMD) response in the brachial artery of patients. Accordingly we aimed to measure endothelium dependent and independent functions of brachial artery in patients with and without significant coronary artery disease. Subjects and Methods: The study included 21 patients (Group I: 52.9짹14.5years, 11 males) with headache, and 50 patients (Group: 56.3짹9.4 years, 32 males) without headache and new onset of chest pain. Patients were excluded from this study if they had a history of chronic headache, long term nitrates use, coronary artery disease-related procedures. Coronary angiography was performed within one month of NTG administration with the usual clinical indications. Clinical characteristics, inflammatory markers including high sensitivity C-reactive protein (hs-CRP) and white blood cell (WBC) count and flow-mediated dilation (FMD), and NMD were compared between the two groups. FMD and inflammatory markers were measured in the morning before CAG. Results: The clinical characteristics and FMD did not differ between the two groups. The NMD was significantly higher in Group I than in Group II (23.2짹7.26% vs. 18.4짹7.0%, p=0.010). The levels of fibrinogen significantly higher in Group I than in Group II (305.3짹71.5 mg/dL vs. 247.2짹82.6 mg/dL, p=0.011). Thirty percentage of patients reported headache after NTG administration. In patients with normal coronary or minimal CAD, 50% had headache caused by sublingual NTG, whereas in patients with significant obstructive CAD, only 3% had headache after NTG use (p <0.001). Conclusion: We have shown that NTG- induced headache have significantly increased NMD. NTG-induced headache develops in patients with normal coronary arteries or minimal CAD than in patients with obstructive CAD.