Background <p>Non-ST-elevation myocardial infarction (NSTEMI) is conventionally attributed to subtotal or transient occlusion. ECG is crucial but has limited sensitivity for detecting acute total occlusion in patients with NSTEMI. We propose that speckle tracking echocardiography-derived indices serve as early indicators of coronary artery occlusion in NSTEMI.</p> Methods <p>In this case–control study, 47 patients with first-time hemodynamically stable NSTEMI were enrolled and underwent echocardiography and coronary angiography. Patients were divided into acute occlusion and non-occlusion groups for analysis. Reproducibility analysis was done in a separate cohort of 22 patients with each patient undergoing three sets of strain echocardiography analysis: twice by the principal observer on two different instances (for intra-observer reproducibility) and once by second observer on the first instance (for inter-observer reproducibility).</p> Results <p>The study included 24 cases (patients with acute total occlusion) and 23 controls (patients without acute total occlusion). There was no difference between the two groups in relation to baseline characteristics. Left-ventricular global longitudinal strain (GLS) did not differ significantly between the two groups. Median longitudinal strain (LS) of the culprit artery territory was significantly lower in the cases group [8.1(7.1–12.6) vs 11.6(10.9–14.1), and <i>p</i> = 0.003]. The lowest recorded mean territorial (LRMT) LS of any territory in a given patient was significantly lower in the cases group compared to the control group [8.1(6.7–12.1) vs. 11(10.2–13), <i>p</i> = 0.04). The receiver–operator curve of LRMT LS showed an area under the curve of 0.74. A cut-off value 10.7 for LRMT LS had a sensitivity of 70.8% and specificity of 70% in detecting acute total occlusion. Reproducibility analysis of GLS and territorial strain (each territory separately) showed moderate-to-good [interclass correlation coefficient (ICC)) of ≥ 0.5] inter-observer and intra-observer reproducibility in most of parameters except in territorial strain of left circumflex artery territory which showed poor intra-observer reproducibility (ICC of 0.49).</p> Conclusion <p>The lowest recorded mean territorial LS in patients with NSTEMI showed promising sensitivity and specificity in detecting acute total occlusion.</p>