Background: High mechanical index impulse of ultrasound is used for diagnosis of microvascular coronary obstruction and the necrotic area, but an experimental model study suggested that it can restore microvascular and epicardial coronary flow. The purposes of the study were to test the safety and therapeutic efficacy of high acoustic energy diagnostic ultrasound in patients with ST-segment elevation myocardial infarction. Material/Methods: Patients with ST-segment elevation myocardial infarction subjected to a low (n=199) or high (n=251) mechanical index ultrasound before and after percutaneous coronary interventions and echocardiographic parameters were evaluated. Coronary angiographies were performed for the assessment of culprit vessels. Thrombolysis in myocardial infarction flow grade 1 or 2 were considered as culprit vessels. Results: Patients diagnosed through low acoustic energy ultrasound reported 235 infarct vessels and patients diagnosed through high acoustic energy ultrasound reported 300 infarct vessels. With respect to low acoustic energy, high acoustic energy reduced the number of culprit vessels at post-percutaneous coronary interventions at 48 hours before hospital discharge (P=0.015) and post-percutaneous coronary interventions at 1-month from the baseline interventions (P=0.043). Also, the maximum% ST-segment resolution and an ejection fraction of the left ventricle was increased and microvascular coronary obstruction in infarct vessels was decreased for both evaluation points. High acoustic energy could not affect heart rate (P=0.133) and oxygen saturation (P=0.079). Conclusions: High acoustic energy ultrasound is a safe method for diagnosis of ST-segment elevation myocardial infarction and may have therapeutic applications.