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Background: Wellens’ sign (WS) has been reported as a sign of critical proximal left anterior descending (PLAD) artery lesion with lumen narrowing greater than 90%. Wellens’ ECG signs for critical PLAD lesion are characterized by two different electrocardiogram (ECG) patterns: 1) Deep T wave inversion in leads V2, V3 (approximately 76% of cases); and 2) Biphasic T wave in leads V2, V3 (approximately 24% of cases). The prevalence of the ECG feature of WS ranges from 14-18%. The prognostic significance of WS in detecting significant coronary artery lesion defined as a luminal narrowing of the coronary vessel by more than 70% has not been well studied. Our study’s goal was to evaluate if WS is present in all patients with critical and significant PLAD lesions and is a sensitive or specific sign for critical and significant (>70% stenosis) PLAD lesions. Methods: All patients that underwent percutaneous coronary intervention (PCI) at an urban community hospital between January 2009 and December 2011 were included in the study. Log books from the cardiac catheterization laboratory were reviewed for all lesion types and corresponding demographics. The ECGs of patients with PLAD lesion were reviewed for T wave changes in precordial leads. Additionally, demographics such as age, gender and cardiovascular risk factors were recorded and analyzed. Descriptive statistics were used to analyze the data. Results: A total of 431 patients underwent PCI [emergent PCI 152 (35.3%), elective PCI 279 (64.7%)]. A total of 78 patients (18.1%) from both groups were found to have PLAD lesion. Fifty eight patients were male and 20 patients were female. The average age was 63.7 years. Critical PLAD lesion was present in 26 patients (33.3%) and 52 patients (66.7%) had PLAD lesion less than 90%. Of the 26 patients, 17 (65.4%) had WS. Wellens’ sign for predicting a critical PLAD had a sensitivity of 65.4%, a specificity of 69.2%, a positive predictive value (PPV) of 51.5% and a negative predictive value (NPV) of 80% (p = 0.0069, two-tailed Fisher’s exact test). Of the 42 patients who had PLAD lesion greater than 70%, 21 patients (50%) had WS. Of the 36 patients who had PLAD lesion less than 70%, 11 patients (30.6%) had WS. Wellens’ sign for predicting significant PLAD lesion in this cohort has a sensitivity of 50%, a specificity of 69.4%, a PPV of 65.6% and a NPV of 54.3% ( p = 0.1074). Conclusion: Our results corroborated prior studies showing that WS predicts the presence of critical (90%) PLAD lesion. Unfortunately, the value of WS for detecting/predicting significant CAD in PLAD was weak. Our results indicated that we were not able to predict the presence of significant (70%) PLAD lesion using WS. However, in appropriate clinical settings such as Non-ST elevation MI (NSTEMI) or unstable angina, Wellens’ sign may indicate the need for a more aggressive treatment strategy with patients proceeding to the cardiac catheterization suite sooner than later.