BACKGROUND Endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA) for the diagnosis of mediastinal and hilar lymph is poorly studied in patients with extrathoracic malignancies.AIM To evaluate the value of EBUS-TBNA for the diagnosis of enlarged intrathoracic lymph nodes in patients with extrathoracic malignancies.METHODS This was a retrospective study of patients with extrathoracic malignancies who were referred to Peking University Cancer Hospital from January 2013 to December 2018 for EBUS-TBNA due to intrathoracic lymphadenopathy. The specimens were defined as positive for malignancy, negative for non-malignancy(tuberculosis, sarcoidosis, etc.), and without a definitive diagnosis. Sensitivity, negative predictive value(NPV) for malignancy, and overall accuracy were calculated. Complications were recorded.RESULTS A total of 80 patients underwent EBUS-TBNA and had a final diagnosis, among which 50(62.5%) were diagnosed with extrathoracic malignancy with intrathoracic lymph nodes metastasis, 14(17.5%) were diagnosed with primary lung cancer with nodal involvement, and 16(20.0%) exhibited benign behavior including tuberculosis, sarcoidosis and reactive lymphadenitis or who had benign follow-up. The diagnostic sensitivity, NPV, and accuracy of EBUS-TBNA for intrathoracic lymphadenopathy in patients with extrathoracic malignancy were 93.8%(n = 60/64), 80.0%(n = 16/20), and 95.0%(n = 76/80), respectively. In the multivariate analysis, longer short axis of the lymph node(OR: 1.200, 95%CI: 1.024-1.407; P = 0.024) and synchronous lung lesion(OR: 19.449, 95%CI: 1.875-201.753; P = 0.013) were independently associated with malignant intrathoracic lymphadenopathy. No characteristics of the lymph nodes and EBUS-TBNA were associated with the location of malignant intrathoracic lymphadenopathy, and no major complication was observed.CONCLUSION EBUS-TBNA is a simple and accurate procedure for the diagnosis of intrathoracic lymphadenopathy with extrathoracic malignancy.