Electrocardiographic Decision Support – Myocardial Ischaemia (EDS-MI) is a graphical decision support for detection and localization of acute transmural ischaemia. A recent study indicated that EDS-MI performs well for detection of acute transmural ischaemia. However, its performance has not been tested in patients with non-ischaemic ST-deviation. We aimed to optimize the diagnostic accuracy of EDS-MI in patients with verified acute coronary occlusion as well as patients with non-ischaemic ST deviation and compare its performance with STEMI criteria. We studied 135 patients with non-ischaemic ST deviation (perimyocarditis, left ventricular hypertrophy, takotsubo cardiomyopathy and early repolarization) and 117 patients with acute coronary occlusion. In 63 ischaemic patients, the extent and location of the ischaemic area (myocardium at risk) was assessed by both cardiovascular magnetic resonance imaging and EDS-MI. Sensitivity and specificity of ST elevation myocardial infarction criteria were 85% (95% confidence interval (CI) 77, 90) and 44% (95% CI 36, 53) respectively. Using EDS-MI, sensitivity and specificity increased to 92% (95% CI 85, 95) and 81% (95% CI 74, 87) respectively (p=0.035 and p<0.001). Agreement was strong (83%) between cardiovascular magnetic resonance imaging and EDS-MI in localization of ischaemia. Mean myocardium at risk was 32% (± 10) by cardiovascular magnetic resonance imaging and 33% (± 11) by EDS-MI when the estimated infarcted area according to Selvester QRS scoring was included in myocardium at risk estimation. In conclusion, EDS-MI increases diagnostic accuracy and may serve as an automatic decision support in the early management of patients with suspected acute coronary syndrome. The added clinical benefit in a non-selected clinical chest pain population needs to be assessed.