Background: Persistent T-wave inversion (PTI) after ST-elevation myocardial infarction (STEMI) is associated with worse clinical outcome; however, the underlying mechanism between PTI and poor prognosis is incompletely understood. We sought to investigate the relationship between PTI and myocardial damage assessed by cardiac magnetic resonance (CMR) following STEMI. Methods: In this prospective observational study, we included 142 consecutive revascularized STEMI patients. Electrocardiography to determine the presence and amplitude of PTI and pathological Q-waves was conducted 4months after infarction. CMR was performed within 1 week after infarction and at 4 months follow-up to evaluate infarct characteristics and myocardial function. Results: Patients with PTI (n = 103, 73%) showed a larger acute (21[11-29] vs. 6[1-13]%; p < 0.001) and chronic infarct size (IS) (14[8-19] vs. 3[1-8]%; p < 0.001) and more frequently microvascular obstruction (59 vs. 33%; p = 0.02). The association between PTI and chronic IS remained significant (odds ratio: 9.02, 95% CI 3.49-23.35; p < 0.001) after adjustment for pathological Q-wave and other IS estimators (high-sensitivity cardiac troponin T and C-reactive protein, N-terminal pro B-type natriuretic peptide, culprit vessel, pre-interventional TIMI flow). The value of PTI amplitude for the prediction of large chronic IS > 11% (AUC: 0.84, 95% CI 0.77-0.90) was significantly higher compared to Q-wave amplitude (AUC: 0.72, 95% CI 0.63-0.80; p = 0.009); the combination of PTI with pathological Q-wave (Q-wave/T-wave score) led to a net reclassification improvement of 0.43 (95% CI 0.29-0.57; p < 0.001) as compared to PTI alone. Conclusions: PTI following STEMI is independently and incrementally associated with more extensive myocardial damage as visualized by CMR. An electrocardiographic score combining PTI with pathological Q-wave allows for a highly accurate IS estimation post-STEMI. (C) 2017 Elsevier B.V. All rights reserved.