Abstract Background Evaluation of cardiac function is crucial for management of patients with acute myocardial infarction (AMI). Recently, high frame rate (HFR) echocardiography has enabled identification of fast-propagating mechanical waves (MW) within the myocardium. These waves have the potential to offer unique insights into myocardial tissue properties, including edema and fibrosis. However, the potential of 3D HFR echocardiography to accurately quantify MW velocities and thereby assess myocardial stiffness in AMI patients remains unexplored. Purpose To assess the feasibility of a novel method for estimating MW velocities using 3D HFR echocardiography in patients with AMI compared to healthy controls. Methods Twenty patients with first time ST-elevation myocardial infarction were included within 48 hours after reperfusion therapy. We used a commercially available ultrasound scanner to acquire conventional 3D high-quality (~20 frames per second) acquisitions and subsequent 3D HFR recordings (~820 frames per second). The high-quality recording was used to extract a myocardial mask to define the region of interest in the HFR acquisition to detect the atrial kick wave and generate a comprehensive 3D map of MW propagation and velocities. We compared MW velocities between these patients and twenty age- and sex-matched healthy controls. Results MW velocities were successfully measured in 93% of participants (17 patients and 20 controls). Global MW velocities were significantly higher in AMI patients compared to healthy controls (2.1±0.6m/s vs. 1.5±0.2m/s, p<0.001). Territorial values, corresponding to the theoretical perfusion area of the three main coronary arteries, were significantly higher in infarct-related territories in patients when compared to same territories in controls for all coronary territories: Right coronary artery: 1.9±0.7 m/s vs. 1.4±0.3m/s, p<0.05; Circumflex artery: 3.1±1.5m/s vs. 1.7±0.4m/s, p<0.01; and Left anterior descending artery: 1.8±0.5m/s vs. 1.4±0.2m/s, p<0.01. Conclusions Estimation of MW velocities using a novel 3D HFR echocardiography method was feasible in most patients with AMI and all healthy controls. MW velocities were higher in patients compared to healthy controls and infarcted compared to non-infarcted coronary territories. These findings confirm the potential of non-invasive myocardial tissue characterization by MW imaging.Boxplot of MW velocities3D HFR MW visualisation