No-reflow (NR) is one of the major complications of primary percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We aim to assess the value of multilayer longitudinal strain parameter to predict NR in patients with NSTEMI and preserved ejection fraction. 230 consecutive patients who were admitted to the emergency department and diagnosed with NSTEMI were prospectively included in this study. Echocardiography was performed 1 h before angiography. Specific analysis for endocardial, mid-myocardial and epicardial layers were performed by two-dimensional (2D) speckle tracking echocardiography (STE) for multilayer longitudinal strain. NR was described as flow grade of <= TIMI 2 when mechanical occlusions like dissection, intimal tear, arterial spasm and thromboembolism during angiography were excluded. 49 of 168 patients admitted to the study had NR. No significant differences were observed between the groups regarding age and gender. Multilayer longitudinal strain imaging (endocard, midmyocard and epicard) revealed lower strain values particularly in endocardial layer in patients with NR (GLS-endocard: - 14.14 +/- 1.39/- 17.41 +/- 2.34, p < 0.001; GLS-midmyocard: - 14.81 +/- 1.40/17.81 +/- 2.22, p < 0.001; GLS-epicard: - 16.14 +/- 1.38/18.22 +/- 2.00, p < 0.001). GLS-endocard, GLS-midmyocard, GLS-epicard and ST depression were found to be statistically significant independents parameters respectively to predict NR phenomenon (GLS-endocard: OR: 2.193, p < 0.001; GLS-midmyocard: OR: 1.510, p: 0.016; GLS-epicard: OR: 1.372, p: 0.035; ST depression: OR: 3.694, p: 0.014). We revealed that left ventricular strain study with speckle tracking echocardiography predicts NR formation. This noninvasive method may be useful for detecting NR formation in patients with NSTEMI.