Background: Left main coronary artery (LMCA) disease is a critical condition with high mortality, necessitating rapid and accurate diagnosis. ST-segment elevation in lead aVR (STEaVR) has been proposed as a specific electrocardiographic (ECG) marker for significant LMCA obstruction. Objective: To evaluate the predictive value of STEaVR for identifying significant LMCA disease in Bangladeshi population. Methods: This prospective cross-sectional study was conducted at Ibn Sina Medical College Hospital, Dhaka, from July 2024 to June 2025. A purposive sample of 87 patients presenting with suspected acute coronary syndrome and undergoing coronary angiography was enrolled. The presence of ≥0.5 mm STEaVR was identified on the admission ECG. Significant coronary artery disease was defined as ≥50% stenosis of the LMCA or ≥70% in other major epicardial vessels. Data were analyzed using SPSS version 23.0. Results: Significant LMCA disease was identified in 27.6% (24/87) of patients. ST-segment elevation in lead aVR (STEaVR) demonstrated a sensitivity of 79.2% and a specificity of 82.5% for predicting LMCA obstruction. The positive and negative predictive values were 63.3% and 91.2%, respectively. The presence of STEaVR was associated with 18-fold increased odds of LMCA disease (OR: 18.0, 95% CI: 5.87-55.18, p<0.001). Conclusion: STEaVR is a highly specific predictor of critical left main coronary artery disease. Its presence on ECG should prompt urgent coronary angiography. This simple marker is invaluable for rapid risk stratification and guiding immediate intervention.