BACKGROUND: It is crucial to timely recognize individuals presenting high-risk characteristics indicative of acute myocardial infarction. OBJECTIVES: Our study aimed to analyze the significance of evaluating ST-segment depression in patients with acute inferior myocardial infarction (MI). We assessed precordial ST-T changes as an indicator of ongoing ischemia, examined their correlation with the extent of coronary artery involvement, and potential association with both early and late cardiac outcomes. METHODS: We enrolled 200 hospitalized patients with acute inferior MI who displayed ST depression in their precordial leads and underwent angiography. Individuals were divided into three groups based on the location of ST depression (V1-V3, V4-V6, and V1-V6). Demographic and echocardiographic data were extracted, and cardiac outcomes were assessed during hospitalization and follow-ups. RESULTS: The findings revealed significant associations between ST depression in leads V1-V6 and V4-V6 with left ventricular systolic dysfunction, mitral regurgitation severity, and the extent of coronary artery stenosis in comparison with ST depression in V1-V3 ( CONCLUSION: Greater ST-segment depression in V1-V6 and V4-V6 in comparison with V1-V3 may signal multivessel disease, severe ischemia. Adverse outcomes like heart failure showed in V1-V6 especially V1-V3 versus V4-V6. This ST depression in acute inferior MI patients could indicate simultaneous ischemia or necrosis in other left ventricle regions, worsening cardiac function and prognosis. Thus, timely interventions are crucial.