OBJECTIVE The diagnostic yield of flexible fiberoptic bronchoscopy for peripheral lung cancers is still limited. This study evaluated whether endobronchial ultrasound (EBUS) may help localize and improve the diagnostic yield of bronchoscopic transbronchial lung biopsy in peripheral lung cancer. METHODS Between July 2001 and May 2002, 218 patients received transbronchial lung biopsy during bronchoscopic examinations with (n = 122) or without EBUS guidance (n = 96) and had the presence of peripheral lung cancers subsequently confirmed. These 218 patients were included in this retrospective analysis. RESULTS The diagnostic accuracy of transbronchial lung biopsy was significantly increased under EBUS guidance for small cell carcinoma (65.6%) and for non-small cell carcinoma (42.7%) [p < 0.01]. For peripheral lung cancer either smaller than 2 cm or larger than 2 cm, the diagnostic yield of transbronchial lung biopsy with EBUS guidance was significantly higher (66.0% vs 42.3%, p < 0.002 for mass larger than 2 cm; 54.5% vs 0%, p < 0.04 for mass smaller than 2 cm). EBUS provided a better diagnostic yield (p = 0.014; odds ratio, 0.219) for lesions localized at the left upper lobe, which are generally thought to be more difficult to approach through bronchoscopy. There were no significant differences in complications between patients who underwent bronchoscopy with or without EBUS guidance. CONCLUSIONS Under EBUS guidance, the diagnostic yield of transbronchial lung biopsy in peripheral lung cancer by bronchoscopic examination was significantly improved without difference in the complication rate.