Objectives: To investigate the predictive value of four-dimensional (4D) strain echocardiography for major adverse cardiovascular events (MACE) in ST-elevation acute myocardial infarction (STEMI) patients. Methods: Consecutive STEMI patients who underwent successful primary coronary interven tion (PCI) were enrolled and followed, with 2D and 4D strain echocardiography performed within 1 week after PCI. Results: Twenty-six first MACE were recorded in 81 patients who finished a ∼3.0 year follow-up. Compared with those without MACE, subjects with MACE were more likely to have anterior MI (73.08 vs. 38.18%, p = 0.003), significantly decreased 2D left ventricular ejection fraction (2DLVEF) and 4DLVEF (all p < 0.05), as well as an overtly compromised 4D strain parameters. The prediction models incorporating infarct location with either 2DLVEF or 4D strain parameters were then developed. Model comparisons revealed that the global area strain (GAS)-based model had the highest discriminative capacity (c statistics = 0.774) and was well calibrated for MACE. Additionally, the clinical utility of the GAS-based prediction model was verified by decision curve analysis showing a consistent positive and larger net benefit compared to the 2DLVEF-based model. Conclusions: Our data support a superiority of 4D strain echocardiography over conventional 2D echocardiography, especially GAS, for risk stratification in STEMI patients after successful primary PCI.