Negative T waves in precordial leads are often seen in patients with acute coronary syndrome (ACS), but also occur in those with acute pulmonary embolism (APE). However, little attention has been given to differences in negative T waves between patients with these 2 diseases. The present study examines the value of electrocardiograms for discriminating between 40 patients with APE and 87 patients with ACS who had negative T waves in the precordial leads (V₁ to V₄) on the admission electrocardiogram. In 77 patients (89%) with ACS, the culprit lesion was confirmed angiographically to be located in the left anterior descending coronary artery. Pulmonary P waves, S₁S₂S₃ pattern, S₁Q₃T₃ pattern, low voltage, and clockwise rotation were specific for APE, but sensitivities of these findings were very low. In patients with APE, negative T waves were commonly present in leads II, III, aVF, V₁, and V₂, but were less frequent in leads I, aVL, and V₃ to V₆ (p <0.05). Negative T waves in leads III and V₁ were observed in only 1% of patients with ACS compared with 88% of patients with APE (p <0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of this finding for the diagnosis of APE were 88%, 99%, 97%, and 95%, respectively. In conclusion, the presence of negative T waves in both leads III and V₁ allows APE to be differentiated simply but accurately from ACS in patients with negative T waves in the precordial leads.