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The diagnosis of mediastinal and hilar lymphadenopathy and staging lung cancer with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are on the rise. Most reports have demonstrated high yields with EBUS-TBNA and superiority of this procedure over conventional TBNA (cTBNA), but the relative roles of these procedures remain undefined. We present a comprehensive comparison of EBUS-TBNA to cTBNA.We reviewed all of the bronchoscopies performed at our medical center from January 2009 through December 2010. We collected data on 82 EBUS-TBNAs and 209 cTBNAs performed. A cost analysis was subsequently performed.EBUS-TBNA was performed more often in patients with known prior cancer and suspicion of recurrence or staging compared with cTBNA (42% vs 18%, P < 0.001). cTBNA was more likely to be performed in patients suspected of having malignancy and needing diagnostic specimens (70% vs 46%, P = 0.009). The overall yield in which a diagnostic specimen or lymphoid tissue was obtained was not different in each group: EBUS 84% vs cTBNA 86% (P = 0.75). The cancer yield was 57% in cTBNAs compared with 44% in EBUS-TBNAs (P < 0.0001), with EBUS-TBNA more often targeting smaller nodes (mean 15 ± 7 mm vs 21 ± 11 mm; P < 0.0001) and paratracheal sites (67% vs 49%, P = 0.003). Per-procedure cost using a Medicare scale was higher for EBUS than it was for cTBNA ($1195 vs $808; P < 0.001).EBUS-TBNA and cTBNA are complementary bronchoscopic procedures, and the appropriate diagnostic modality can be selected in a cost-effective manner based upon the primary indication for TBNA, lymph node size, and lymph node location.