Objectives: To examine the hypothesis that glyceryl trinitrate(GTN) may cause headache in patients with normal coronary arteries more often than in patients with obstructive coronary artery disease(CAD). This simple assessment may aid clinicians in the initial evaluation of chest pain syndrome and possible CAD. Patients and methods: 118 patients(66 men and 52 women) with new onset of chest pain were enrolled in this study. Patients were excluded from the study if they had a history of chronic headache, long term nitrates use, or any coronary artery procedures. Mean age of the patients was 62.5 years. Coronary angiography was performed within one month of GTN administration with the usual clinical indications such as recurrent chest pain, abnormal ECG, or abnormal results of stress tests. Thirty patients had normal coronary arteries or minimal or non-obstructive CAD. Eighty eight patients had obstructive CAD defined as luminal narrowing greater than 50%in any one or more of the left or right coronary arteries or their major branches. All the patients had a varying degree of relief of chest pain with GTN administration within 10 minutes. 36%of patients reported significant headache after GTN administration. Results: In patients with normal coronary arteries or minimal CAD, 73%had significant headache caused by sublingual GTN. In patients with obstructive CAD, only 23%had significant headache after GTN use(p< 0.001). There were no differences in patientssex and vascular risk factors concerning the frequency of headache in patients with or without obstructive CAD. Conclusions: GTN causes significantly more frequent headache episodes in patients with normal coronary arteries or minimal CAD than in patients with obstructive CAD. This unique finding may provide clinicians with an additional tool for the differential diagnosis of patients with chest pain syndrome. Objectives: To examine the hypothesis that glyceryl trinitrate (GTN) may cause headache in patients with normal coronary arteries more often than in patients with obstructive coronary artery disease (CAD). This simple assessment may aid clinicians in the initial evaluation of chest pain syndrome and Possible CAD. Patients and methods: 118 patients (66 men and 52 women) with new onset of chest pain were enrolled in this study. Patients were excluded from the study if they had a history of chronic headache, long term nitrates use, or any Coronary angiography was performed within one month of GTN administration with the usual clinical indications such as recurrent chest pain, abnormal ECG, or abnormal results of stress tests. Thirty patients had normal coronary arteries or minimal or non-obstructive CAD. Eighty eight patients had obstructive CAD defined as luminal narrowing greater than 50% in any one or more of the left or All coronary patients had a varying degree of relief of chest pain with GTN administration within 10 minutes. 36% of patients reported significant headache after GTN administration. Results: In patients with normal coronary arteries or minimal CAD, 73% had significant headache caused by sublingual GTN. In patients with obstructive CAD, only 23% had significant headache after GTN use (p <0.001). There were no differences in patients? Xx and vascular risk factors concerning the frequency of headache in patients with or without obstructive CAD. Conclusions: GTN causes significantly more frequent headache episodes in patients with normal coronary arteries or minimal CAD than in patients with obstructive CAD. This unique finding may provide clinicians with an additional tool for the differential diagnosis of patients with chest pain syndrome.