We conducted a prospective multi-institutional clinical study involving community hospitals and academic medical centers to more carefully define the value of computerized tomography (CT) of the chest with transbronchial needle aspiration (TBNA) in the staging of bronchogenic carcinoma (CA), and to assess the predictors of a positive aspirate. Of 360 individuals determined to have bronchogenic carcinoma, 50 of 81 (62%) with small cell carcinoma (SCC) and 135 of 279 (48%) with non-small cell carcinoma (NSCC) had positive aspirates (p = 0.034). TBNA precluded additional thoracic surgery in a total of 104 of 360 (29%) patients and was exclusively diagnostic of carcinoma in 65 of 360 (18%) cases. Right-sided tumors were more likely to have a positive mediastinal TBNA (p = 0.002 to 0. 01) as were histologic (67 of 118 [57%]) rather than cytology aspirates (228 of 532 [41%]) (p < 0.001). Sensitivity was > 57% in lymph nodes (LN) >/= 10 mm, and among LN of equivalent size, right paratracheal and subcarinal sites were most likely to establish malignancy. Preoperative CT is a valuable adjunct in the staging of CA by TBNA. Increasing LN size, right-sided tumors, right paratracheal and subcarinal locations, use of a histology needle, and the presence of SCC are the best predictors of a positive aspirate.