Background: Three-dimensional speckle-tracking echocardiography (3D-STE) allows simultaneous assessment of multidirectional components of strain. However, there are few data on its usefulness to predict prognosis in patients with acute myocardial infarction (AMI). The objective of our pilot study was to evaluate the prognostic value of four different 3D-STE parameters (global longitudinal strain (GLS-3D), global circumferential strain (GCS-3D), global radial strain (GRS-3D), and global area strain (GAS)) in AMI, after successful revascularization by primary PCI. Methods: We enrolled 94 AMI patients (66 ± 13 years, 56% men) who underwent coronary angiography. All patients had been 3D-STE assessed and followed-up for 1 year for the occurrence of MACE. Results: A total of 25 MACE were recorded over follow-up. Cut-off values of −17% for GAS (HR = 3.1, 95% CI: 1.39–6.92, p = 0.005), −12% for GCS-3D (HR = 3.06, 95% CI: 1.36–6.8, p = 0.006), −10% for GLS-3D (HR = 3.04, 95% CI: 1.36–6.78, p = 0.006), and 25% for GRS-3D (HR = 2.89, 95% CI: 1.29–6.46, p = 0.009) showed moderate accuracy in MACE prediction. Multivariate regression showed that GAS (HR = 1.1, 95% CI: 1.03–1.16), GLS-3D (HR = 1.13, 95% CI: 1.03–1.26), and GCS-3D (HR = 1.13, 95% CI: 1.03–1.23) remained independent predictors of MACE (HR = 1.07, 95% CI: 1.01–1.14 for GAS, and HR = 1.1, 95% CI: 1.01–1.2 for GCS-3D). However, post hoc power analysis indicated adequate sample size (power of 80%) only for GAS and GCS-3D for the ROC curve analysis and for GAS, GCS-3D, and GRS-3D for the log-rank test. Conclusion: Patients with AMI might benefit from early risk stratification with the aid of 3D-STE measurements, particularly GAS and GCS-3D, but larger studies are necessary to determine the optimal cut-off values to predict MACE.