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Management of patients with coronary artery disease is a major challenge for physicians, patients, and the healthcare system. Chest pain experienced by patients with coronary disease can be of noncardiac origin, and symptoms frequently related to gastroesophageal etiologies. The distal esophagus and the heart share a common afferent nerve supply, suggesting that location and radiation of perceived pain may be identical. In addition, there is substantial overlap between the prevalence of coronary disease and gastroesophageal reflux disease. Many physicians, including cardiologists, prescribe acid-reducing therapy to coronary patients. However, no prospective, randomized studies to date have evaluated the potential benefit of such treatments to prevent chest pain symptoms for these patients. We review the studies on noncardiac chest pain demonstrating reflux in patients with and without coronary disease. Also, the association of reflux with exertional chest pain and cardiac syndrome X is discussed. A rationale is presented for prevention of noncardiac chest pain in coronary patients, and the potential role of acid-suppressive therapy in managing these patients is discussed.