Criteria for electrocardiographic detection of acute myocardial ischemia recommended by the Consensus Document of ESC/ACCF/AHA/WHF consist of two parts: The ST elevation myocardial infarction (STEMI) criteria based on ST elevation (ST↑) in 10 pairs of contiguous leads and the other on ST depression (ST↓) in the same 10 contiguous pairs. Our aim was to assess sensitivity (SE) and specificity (SP) of these criteria-and to seek their possible improvements-in three databases of 12‑lead ECGs. We used (1) STAFF III data of controlled ischemic episodes recorded from 99 patients (pts) during percutaneous coronary intervention (PCI) involving either left anterior descending (LAD) coronary artery, right coronary artery (RCA), or left circumflex (LCx) coronary artery. (2) Data from the University of Glasgow for 58 pts with acute myocardial infarction (AMI) and 58 pts without AMI, as confirmed by MRI. (3) Data from Lund University retrieved from a centralized ECG management system for 100 pts with various pathological ST changes-other than acute coronary occlusion-including ventricular pre-excitation, acute pericarditis, early repolarization syndrome, left ventricular hypertrophy, and left bundle branch block. ST measurements at J-point in ECGs of all 315 pts were obtained automatically on the averaged beat with manual review and the recommended criteria as well as their proposed modifications, were applied. Performance measures included SE, SP, positive predictive value (PPV), and benefit-to-harm ratio (BHR), defined as the ratio of true-positive vs. false-positive detections. We found that the SE of widely-used STEMI criteria can be indeed improved by the additional ST↓ criteria, but at the cost of markedly decreased SP. In contrast, using ST↑ in only 3 additional contiguous pairs of leads (STEMI13) can boost SE without any loss of SP. In the STAFF III database, SE/SP/PPV were 56/98/97% for the STEMI, 79/79/79% for the STEMI with added ST↓ and 67/97/96% for the STEMI13. In the Glasgow database, corresponding SE/SP/PPV were 43/98/96%, 84/90/89%, and 55/98/97%. For the Lund database, SP was 56% for the STEMI, 24% for the STEMI with ST↓, and 56% for the STEMI13. Current recommended criteria for detecting acute myocardial ischemia, involving ST↓, boost SE of widely-used STEMI criteria, at the cost of SP. To keep the SP high, we propose either the adjustment of threshold for the added ST↓ criteria or a selective use of ST↓ only in contiguous leads V2 and V3 plus ST↑ in lead pairs (aVL, -III) and (III, -aVL).