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In reperfusion strategy for ST-elevation myocardial infarction (STEMI), emergency surgical bypass grafting might be considered for patients with significant multivessel coronary diseases complicated by cardiogenic shock. The culprit lesions in STEMI can be predicted from electrocardiographic (ECG) findings. However, whether the complexity of coronary artery lesions in STEMI can be predicted from characteristic ECG findings remained unclear.The initial 12-lead ECG parameters in each lead recording from patients with STEMI receiving primary percutaneous coronary intervention within 12 hours were retrospectively analyzed. A sequential ECG algorithm was developed to predict the complexity of coronary artery lesions.In patients with inferior wall STEMI, the presence of the following 2-step criteria indicated 3-vessel disease (3VD), with a sensitivity of 92.1% and a specificity of 81.8%: (1) ST depression or flat T wave in leads V5 or V6; and (2) ST elevation of more than 2 mm in at least 1 of II, III, aVF, or Q (loss of septal r) without ST elevation in aVR. In patients with anterior wall STEMI, the following criteria indicated 3VD: (1) ST elevation of more than 4 mm in at least 1 of the precordial leads and combined with QRS interval of more than 120 ms; then (2) a flat T wave over aVR, or aVL combined with flat T wave ST depression over lead I or Q wave over all leads II, III, and aVF. This algorithm detects patients with 3VD with a sensitivity of 76.5% and a specificity of 100%. However, when the whole algorithm is completed, the sensitivity can reach up to 88.4% and the specificity can still be 100%.By using this ECG algorithm, 3VD might be distinguished early from single-vessel disease in patients with STEMI for appropriate reperfusion strategy.