Invasive mediastinal biopsy is often necessary in the evaluation of non–small cell lung cancer (NSCLC), and mediastinoscopy has long been considered the reference standard. However, the emergence of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) has resulted in controversy regarding it represents a suitable replacement for mediastinoscopy. We chose to determine the utility of EBUS-TBNA in evaluating the mediastinum in patients with NSCLC.The present study was a retrospective review of a prospective database of consecutive patients with NSCLC who underwent EBUS-TBNA for mediastinal evaluation from 2009 to 2011. The sensitivity, specificity, negative predictive value, and accuracy of EBUS-TBNA are reported. Also reported are the size of the lymph nodes biopsied and the number of instances in which EBUS-TBNA obviated the need for cervical mediastinoscopy.A total of 73 patients had a total of 140 mediastinal stations biopsied using EBUS-TBNA. Of the 73 patients, 30 had benign findings and underwent surgical resection, 1 of whom was found to have stage N2 disease. Of the remaining patients, 42 had a positive result and 1 had nondiagnostic biopsy findings for which malignancy was confirmed by mediastinoscopy. Mediastinoscopy would have changed the tumor stage and treatment planning in only 2 (2.7%) of the 73 patients. Overall, EBUS-TBNA had a sensitivity of 95%, a specificity of 100%, a negative predictive value of 94%, and an accuracy of 97%.EBUS-TBNA might be a feasible option for most patients with NSCLC for whom histologic assessment of the mediastinum is necessary. The rates of nondiagnostic and false-negative biopsy findings using EBUS-TBNA were low, small subcentimeter nodes could be routinely biopsied, and most patients with a radiographically positive mediastinum had their disease pathologically confirmed.