Mediastinal lesions represent a diagnostic challenge and often require invasive approaches. We evaluated the role of radial probe endobronchial ultrasound-directed transbronchial needle aspiration (EBUS-TBNA) in the evaluation of mediastinal lesions. Between March 2005 to February 2006, 30 consecutive patients with enlarged mediastinal lymph nodes from unknown etiologies or suspicious for metastatic bronchogenic carcinoma and mediastinal masses underwent EBUS-TBNA and were clinically followed up. EBUS-TBNA was applied under topical anesthesia, midazolam sedation with a mean dose of 4.6+1.7 mg and prolonged the examination by 14.7 minutes on average. EBUS-directed TBNA was performed in 17 lymph nodes and 13 mediastinal masses, achieving specific diagnosis in 82.3% (14/17) and 84.6% (11/13) of examined lesions, respectively, with an overall yield of 83%. The sensitivity, specificity, and accuracy of EBUS-TBNA in distinguishing benign from malignant mediastinal lesions were 89.4%, 100%, and 93.3%, respectively. EBUS was well tolerated by most of the patients with no TBNA-related complications. In conclusion, EBUS-TBNA of mediastinal lesions is a minimally invasive safe diagnostic technique with high yield, even in the hands of those with initial experience. This initial study is convincing and stimulating for widespread application of EBUS-TBNA in Egyptian bronchoscopy practice.