Many studies have reported the prognostic value of global strain obtained with speckle tracking echocardiography (STE) in patients with acute myocardial infarction (AMI). However, as a novel method derived from STE, layer-specific strain has seldom been evaluated with respect to prediction of AMI outcomes. We sought to investigate the predictive value of layer-specific strain and whether it has incremental value compared with conventional parameters, such as left ventricular ejection fraction and wall motion score index, and STE parameters. Our study was prospective. Ninety-two patients with first-onset AMI were enrolled and underwent echocardiography before coronary intervention for analysis of global and layer-specific strain. Cox proportional hazard ratio (HR) and receiver operating characteristic curve analyses were performed for the prediction of cardiac events and cardiac death. Fifty-three patients have had cardiac events during follow-up. Endocardial longitudinal strain has received relatively higher HRs for risk predictions of both cardiac events (HR = 1.69) and cardiac death (HR = 3.21) adjusted with clinical data. The areas under the receiver operating characteristic curves of the longitudinal strain at the endocardial layer from layer-specific strain were higher than those of global strain and conventional parameters for cardiac event prediction (p ˂ 0.05, all). Layer-specific strain is valuable for cardiac risk prediction after infarction and has incremental values in addition to conventional and global STE parameters. Myocardial damage at the endocardial layer was closely related to outcomes of AMI patients at long-term follow-ups.