Although coronary artery disease (CAD) and heart failure (HF) are separate entities, HF is a common complication of CAD, and both CAD and HF are known causes of wall motion abnormalities (WMA) of transthoracic echocardiography (TTE). Specifically, global hypokinesis on TTE could logically be due to multivessel CAD or non-ischemic cardiomyopathy. The purpose of this study was to investigate the relationship between CAD, HF, and WMA on TTE. A single-center retrospective chart review was conducted of adults who had a resting TTE and cardiac catheterization within 30 days. We analysed the association between global hypokinesis, triple-vessel CAD, and HF diagnosis. Across 754 included patients, there was a positive association between global hypokinesis on TTE and HF diagnosis (P < .001). There was no association between global hypokinesis on TTE and triple-vessel CAD (P = .341), possibly an inverse correlation. The sensitivity of regional (R) WMAs on TTE for diagnosing CAD was generally lower in patients without heart failure (44%), while specificity was higher in these same patients (89%). There was a positive association between global hypokinesis and HF, and a possible inverse correlation between global hypokinesis and triple-vessel CAD. This could be explained by heart failure diagnosis and other diagnoses having a stronger effect on global hypokinesis than any potential effect from triple-vessel CAD. These sensitivity and specificity results for RWMA on CAD, stratified by HF diagnosis and/or global hypokinesis, can be used to inform clinical decision-making in an acute coronary syndrome case with borderline electrocardiography and/or troponin findings.