Superior vena cava syndrome (SVCS) requires a timely histopathological diagnosis for appropriate management. We prospectively evaluated the diagnostic yield and complications of transbronchial needle aspiration (TBNA) among patients with SVCS in a tertiary care university hospital. From February 1996 to April 2000, 27 consecutive patients referred with clinical SVCS without a prior diagnosis underwent flexible bronchoscopy and TBNA. The ultimate diagnoses were small cell carcinoma (SCLC) in 15 patients, non-small cell lung carcinoma (NSCLC) in 11, and non-Hodgkin lymphoma in one patient. TBNA was diagnostic in all 26 patients with bronchogenic carcinoma, but not in lymphoma, which was subsequently diagnosed via thoracotomy. The overall diagnostic yield of TBNA was 96%, and the 95% confidence interval (CI) of diagnostic yield was 80-100%. TBNA solely provided the diagnosis in nine patients with NSCLC (82%), and in seven with SCLC (47%), and confirmed the diagnosis established via forceps biopsy in ten patients. Age, gender, radiological involvement and TBNA site were comparable in cases with and without forceps biopsy. There was no major complication related to either flexible bronchoscopy or TBNA. We concluded that TBNA is safe and has a high diagnostic yield in SVCS caused by bronchogenic carcinoma.