Aims To compare the diagnostic accuracy of speckle tracking echocardiography technique using territorial longitudinal strain (TLS) for the detection of culprit vessel vs. vessel-specific wall motion score index (WMSI) in non-ST-segment elevation–acute coronary syndrome (NSTE-ACS) patients scheduled for invasive coronary angiography (ICA). Methods and results One hundred and eighty-three patients (mean age: 66 ± 12 years, male: 71%) diagnosed with NSTE-ACS underwent echocardiography evaluation at hospital admission and ICA within 24 h. Culprit vessels were left anterior descending (LAD), left circumflex (CX), and right coronary arteries (RCAs) in 38.5%, 39.6%, and 21.4%, respectively. An increase of affected vessels [1-, 2-, and 3-vessel coronary artery disease (CAD)] was associated with increased WMSI and TLS values. There was a statistically significant difference of both WMSI-LAD, WMSI-CX, WMSI-RCA and TLS-LAD, TLS-CX, TLS-RCA of myocardial segments with underlying severe CAD compared to no CAD (P = 0.001 and P Conclusion Territorial longitudinal strain allows an accurate identification of the culprit vessel in NSTE-ACS patients. In addition to WMSI, TLS may be considered as part of routine echocardiography for better clinical assessment in this subset of patients.