Pulmonary embolism (PE), a major cause of morbidity and mortality, remains an elusive diagnosis. Recently investigators have found a new electrocardiographic (ECG) finding, simultaneous T-wave inversions in the anterior and inferior leads, which may distinguish PE from acute coronary syndrome (ACS).Our primary objective was to estimate the prevalence of this finding in PE. We also estimate the inter-rater reliability of this finding, its test characteristics, and assess ECG findings traditionally associated with PE.In this unmatched case-control study, we selected electrocardiograms from patients diagnosed with PE, ACS, and non-cardiac chest pain. Two emergency physicians, blinded to diagnoses, reviewed electrocardiograms for explicitly defined ECG findings. We calculated kappa (K) for inter-rater agreement and estimated prevalence differences (PD) for findings in the PE group vs. pooled control groups.We included 97 patients with PE, 89 with ACS, and 105 with non-cardiac chest pain. A 1-mm T-wave inversion was seen in both III and V 1 in 11/97 (0.113) of patients with PE vs. 9/194 (0.046) controls (PD 0.07 [95% confidence interval (CI) −0.01–+0.14]; K = 0.7). Other criteria for anterior and inferior T-wave inversions were less common in PE (0.04–0.05). Among several other ECG abnormalities tested, only sinus tachycardia (PD 0.20 [95% CI 0.09–0.31]; K = 0.7) and the classic S I Q III T III pattern (PD 0.05 [95% CI −0.01–+0.11]; K = 0.5) statistically distinguished PE and were noted with fair or better inter-rater agreement.In our study, simultaneous T-wave inversions in anterior and inferior leads were associated with PE but are seen in only 4–11% of cases.