Introduction: The no-reflow phenomenon has been described in 20–40% of patients with acute ST-segment elevation myocardial infarction, despite restoration of TIMI 3 myocardial flow. It is associated with adverse left ventricular remodeling and an unfavorable long-term prognosis. Case presentation: A 45-year-old gentleman was admitted one hour after the onset of an acute anterior ST-segment elevation myocardial infarction. Emergency coronary angiography was performed, and a severe stenosis of the left anterior descending artery was identified. The lesion was crossed with a pressure-wire, and a drug-eluting stent was directly implanted, with restoration of TIMI 3 epicardial flow. Predilatation was not performed. Coronary wedge pressure was measured during stent deployment. The mean pressure value was 27 mmHg. However, a tall systolic wave was identified in the morphology of the pressure curve. Myocardial blush grade and ST-segment resolution were concordant with early microvascular obstruction. Similarly, at transthoracic Doppler echocardiography, the flow in the left anterior descending artery revealed the same pattern. An apical left ventricular aneurysm was echocardiographically detected. The MRI described extensive interstitial edema that affected the anterior, septal, and apical regions of the left ventricle. Areas of intramyocardial hemorrhage and microvascular obstruction were also detected. According to recent literature data, the morphology of the coronary wedge pressure wave suggested at least the presence of pre-procedural distal embolization. Conclusions: In the setting of acute myocardial infarction, the integrity of coronary microvasculature is an important issue. The distal coronary pressure wave pattern before primary percutaneous revascularization can be a deciding factor for an early therapeutic approach.