Background and Objectives: We evaluated the utility of a combined approach using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-FNA-B/E) for mediastinal staging of lung cancer. Methods: An EBUS-TBNA database was analyzed retrospectively. EUS-FNA-B/E was performed after EBUS-TBNA when mediastinal lymph nodes were not accessible using EBUS-TBNA or when tissue sampling using EBUS-TBNA alone was inadequate. Results: During the study period, 44 patients were enrolled. EBUS-TBNA and EUS-FNA-B/E were performed on 79 and 52 lymph nodes, respectively. The sensitivity, specificity, and accuracy of mediastinal N staging using EBUS-TBNA alone were 79%, 100%, and 84%, respectively. The sensitivity, specificity, and accuracy of mediastinal N staging using a combination of EBUS-TBNA and EUS-FNA-B/E were 100%, 100%, and 100%, respectively. Significant differences in sensitivity (P=0.008) and accuracy (P=0.004) of mediastinal N staging were evident when EBUS-TBNA alone and the combined procedure were compared. The nodal stage shifted higher after use of the EUS-FNA-B/E procedure in six cases (13%). No serious complication associated with the procedures was noted. Conclusions: Use of a combination of EBUS-TBNA and EUS-FNA-B/E can afford better sensitivity and accuracy of mediastinal N staging compared with use of EBUS-TBNA alone. Such combined procedures should be considered for examination of lesions that are inaccessible or difficult to access by EBUS-TBNA.Background and Objectives: We evaluated the utility of a combined approach using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-FNA-B/E) for mediastinal staging of lung cancer. Methods: An EBUS-TBNA database was analyzed retrospectively. EUS-FNA-B/E was performed after EBUS-TBNA when mediastinal lymph nodes were not accessible using EBUS-TBNA or when tissue sampling using EBUS-TBNA alone was inadequate. Results: During the study period, 44 patients were enrolled. EBUS-TBNA and EUS-FNA-B/E were performed on 79 and 52 lymph nodes, respectively. The sensitivity, specificity, and accuracy of mediastinal N staging using EBUS-TBNA alone were 79%, 100%, and 84%, respectively. The sensitivity, specificity, and accuracy of mediastinal N staging using a combination of EBUS-TBNA and EUS-FNA-B/E were 100%, 100%, and 100%, respectively. Significant differences in sensitivity (P=0.008) and accuracy (P=0.004) of mediastinal N staging were evident when EBUS-TBNA alone and the combined procedure were compared. The nodal stage shifted higher after use of the EUS-FNA-B/E procedure in six cases (13%). No serious complication associated with the procedures was noted. Conclusions: Use of a combination of EBUS-TBNA and EUS-FNA-B/E can afford better sensitivity and accuracy of mediastinal N staging compared with use of EBUS-TBNA alone. Such combined procedures should be considered for examination of lesions that are inaccessible or difficult to access by EBUS-TBNA.