Background: Transesophageal EUS-guided FNA (EUS-FNA) is safe, accurate, and cost effective in staging patients with non-small-cell lung cancer (NSCLC). However, the impact of EUS-FNA on patient survival has not been demonstrated. Objective: To determine the impact of metastatic disease in mediastinal lymph nodes as determined by EUS staging on treatment choice and survival in patients with NSCLC. Design: Retrospective analysis of prospectively collected data. Setting: Tertiary university-based referral center. Patients: Patients with biopsy-proven NSCLC who underwent staging EUS-FNA. The relationship between the EUS nodal status and patient survival was evaluated. Cox proportional hazards models were used to determine the significance of EUS nodal status and patient characteristics on patient survival. Main Outcomes Measurements: Impact of EUS-FNA on therapy and survival in patients with NSCLC. Results: Of 125 patients with NSCLC, EUS-FNA confirmed metastatic disease in 46% of the patients. Patients who were node positive were more likely to receive chemotherapy and/or radiation therapy and were less likely to undergo surgery compared with patients who were node negative (P < .0001). Patients with N2 or N3 disease by EUS-FNA had a shorter survival time than patients who were node negative (P = .004). Adjusting for age, race, and sex, EUS-FNA was the most important predictor of survival of patients with NSCLC in this cohort of patients (hazard ratio 2.34, 95% CI 1.31-4.21). Limitations: Lack of surgical reference standard in all patients and referral to a tertiary center. Conclusions: Patients with node-positive NSCLC as detected by EUS-FNA have a shorter survival time compared with patients who were node negative. They are more likely to receive neoadjuvant therapy and less likely to receive surgery. Preoperative EUS-FNA is a minimally invasive technique that provides important prognostic information in patients with NSCLC. © 2008 American Society for Gastrointestinal Endoscopy.