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Purpose: Regional wall motion abnormality (RWMA) on transthoracic echocardiography (TTE) is used as a clinical decision‐making tool to assess systolic function, but there is limited data regarding the validity of this tool to predict obstructive coronary artery disease (CAD). This study evaluates the utility of RWMA on TTE for detecting obstructive CAD in patients with no prior CAD history. Methods: We retrospectively reviewed charts of adults who underwent resting TTE and coronary angiography within 30 days, analyzing RWMA in relation to angiographic luminal stenosis. Results: Among 754 patients (mean age 62, 60% male), TTE sensitivity varied with timing relative to angiography: 68.7% after angiography versus 49.5% before. In ST‐elevation myocardial infarction (STEMI) patients (n = 126 after vs. n = 4 before), sensitivity was 89.8%. RWMA correlated with CAD severity, particularly in STEMI cases. Conclusions: TTE specificity remains high, but sensitivity varies significantly by timing, with the highest sensitivity in STEMI patients. These findings could refine decision‐making in uncertain STEMI cases, supporting TTE as a valuable adjunctive diagnostic tool. [ABSTRACT FROM AUTHOR]