BACKGROUND The belief that chest pain relief with nitroglycerin indicates the presence of active coronary artery disease is common. However, this hypothesis has not been tested. OBJECTIVE To define the diagnostic and prognostic value of chest pain relief with nitroglycerin. METHODS Prospective observational cohort study. METHODS Urban community teaching hospital. METHODS 459 consecutive patients with chest pain admitted through the emergency department who received nitroglycerin from emergency services personnel or an emergency department nurse. Follow-up was obtained by telephone contact at 4 months. METHODS Chest pain relief was defined as a decrease of at least 50% in patients' self-reported pain within 5 minutes of the initial dose of sublingual or spray nitroglycerin. Active coronary artery disease was defined as any elevated serum enzyme levels, coronary angiography demonstrating a 70% or greater stenosis, or a positive exercise test result. RESULTS Nitroglycerin relieved chest pain in 39% of patients (181 of 459). In patients with active coronary artery disease as the likely cause of their chest pain, 35% (49 of 141) had chest pain relief with nitroglycerin. In contrast, in patients without active coronary artery disease, 41% (113 of 275) had chest pain relief (P > 0.2). Four-month clinical outcomes were similar in patients with or without chest pain relief with nitroglycerin (P > 0.2). CONCLUSIONS These data suggest that, in a general population admitted for chest pain, relief of pain after nitroglycerin treatment does not predict active coronary artery disease and should not be used to guide diagnosis.