The study is aimed at evaluating the real incidence of normal coronary arteries and the role of alternative substrates of myocardial ischemia in patients with acute coronary syndrome (ACS) but with no coronary artery disease (CAD) in a real world secondary care public hospital. The medical records of 941 patients undergoing coronary arteriography for ACS within 48 h of onset between January 1st 2000 and November 1st 2003 were critically reviewed. In 70 patients (7.4%, 35 males, mean age 60 +/- 17.2 years) no CAD was documented. Alternative substrates of acute myocardial ischemia included coronary artery anomalies (7 patients, 10%), coronary spasm (10 patients, 14.3%), spontaneous coronary dissection (2 patients, 2.8%), paradoxical embolism through a patent foramen ovale (4 patients, 5.7%), embolism from left atrium or calcified aortic valve (4 patients, 5.7%), imbalance between oxygen demand and supply (20 patients, 28.5%), mitral valve prolapse (11 patients, 15.7%). No alternative substrates were found in 12 patients (17.1%). Patients with no CAD are more frequently female and younger. Absence of CAD is an uncommon finding in patients undergoing coronary artery angiography for ACS.