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Objective Absence of significant epicardial coronary artery disease (CAD) in patients with acute onset of chest pain and elevation of myocardial necrosis markers is occasionally observed. The aim of this study was to analyse the clinical characteristics and outcome of such patients with advanced age. Methods We retrospectively analysed 4,311 patients with acute onset of chest pain plus necrosis marker elevation. Two hundred and seventy two patients without CAD on angiogram (6.3%) were identified. Out of them, 50 (1.2%) patients ≥ 75 years (Group I) were compared with (1) 222 acute coronary syndrome (ACS) patients without CAD on angiogram < 75 years (Group II), and (2) 610 consecutive patients ≥ 75 years with Non-ST-elevation Myocardial Infarction (NSTEMI) undergoing percutaneous coronary intervention (Group III). Results Group I compared to Group III patients made up for more females (64.0% vs. 49.2%; P < 0.0001), and had more severe anginal symptoms on presentation [Canadian Cardiovascular Society (CCS) class I/II, 26.0% vs. 49.8%; P = 0.02]. Group I patients also had lower troponin levels (0.62 ± 0.8 ng/mL vs. 27 ± 74 ng/mL; P < 0.02), lower leukocyte count (9.4 ± 3.13 × 109 vs. 12 ± 5.1 × 109; P = 0.001) and better preserved left ventricular function (56.7% ± 14.3% vs. 45% ± 11%; P < 0.0001). Event-free survival (cardiac death, myocardial infarction, recurrent angina, and re-hospitalisation) was more frequent in Group I and II patients compared to Group III patients (64.9%, 66.7%, and 41.6%, respectively; P < 0.0001). Conclusions ACS in patients ≥ 75 years without CAD is very infrequent, associated with a (1) similar outcome compared to ACS patients < 75 years without CAD, and (2) significant better outcome compared to NSTEMI patients ≥ 75 years.