INTRODUCTION: Selecting the appropriate treatment strategy for patients with locally advanced non-small cell carcinoma (NSCLC) is of utmost importance to determine patient outcome. Previous studies have shown that nodal down-staging after induction therapy and definitive local irradiation in these patients better predict survival when combined with surgery. However, nodal restaging can be technically difficult. We investigated the role of transbronchial needle aspiration (TBNA) in mediastinal restaging of patients who had completed induction cytotoxic therapy. METHODS: A total of 14 patients with proven stage IIIa-N2 NSCLC who received chemotherapy or chemo-radiotherapy as induction regimen between 2005 and 2006 were studied. Outpatient flexible bronchoscopy with TBNA was performed in all patients under local anesthesia, and 17 TBNA procedures were performed. TBNA results were matched against the histopathology of surgical specimens. RESULTS: Seventeen lymph nodes in 14 patients who had undergone induction therapy were sampled. Positron emission tomography (PET) scan results of 11 patients were also available for comparison. All positive TBNA procedures had positive PET scans. However, for five patients with lymph nodes measuring 9 to 17 mm, the PET scans were falsely positive, as mediastinoscopy and subsequent surgically resected lymph nodes revealed no tumor. TBNA achieved a correct diagnosis in 71% of patients who underwent mediastinal restaging and obviated further need for invasive procedures in 35%. CONCLUSION: For patients presenting with locally advanced NSCLC who are surgical candidates after induction chemo- and/or radiotherapy, TBNA should be considered as the initial procedure of choice for restaging of the mediastinum.