Mediastinal lymph node sampling is a critical step in the staging of lung cancer [1][2][3] and in the diagnosis of infl ammatory conditions, such as sarcoidosis. [4][5][6][7][8] Over the past decade, endobronchial ultrasoundguided transbronchial needle aspiration (EBUS-TBNA) has emerged as a minimally invasive, highly accurate technique for sampling intrathoracic lymph nodes, with a sensitivity of 88% to 93% in distinguishing lymph node metastases from benign conditions. 9,10 Comparative studies have demonstrated the superiority of EBUS-TBNA to conventional TBNA. 11 EBUS-TBNA can reach multiple nodal stations, including Background: Few studies of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been large enough to identify risk factors for complications. The primary objective of this study was to quantify the incidence of and risk factors for complications in patients undergoing EBUS-TBNA. Methods: Data on prospectively enrolled patients undergoing EBUS-TBNA in the American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education (AQuIRE) database were extracted and analyzed for the incidence, consequences, and predictors of complications. Results: We enrolled 1,317 patients at six hospitals. Complications occurred in 19 patients (1.44%; 95% CI, 0.87%-2.24%). Transbronchial lung biopsy (TBBx) was the only risk factor for complications, which occurred in 3.21% of patients who underwent the procedure and in 1.15% of those who did not (OR, 2.85; 95% CI, 1.07-7.59; P 5 .04). Pneumothorax occurred in seven patients (0.53%; 95% CI, 0.21%-1.09%). Escalations in level of care occurred in 14 patients (1.06%; 95% CI, 0.58%-1.78%); its risk factors were age . 70 years (OR, 4.06; 95% CI, 1.36-12.12; P 5 .012), inpatient status (OR, 4.93; 95% CI, 1.30-18.74; P 5 .019), and undergoing deep sedation or general anesthesia (OR, 4.68; 95% CI, 1.02-21.61; P 5 .048). TBBx was performed in only 12.6% of patients when rapid onsite cytologic evaluation (ROSE ) was used and in 19.1% when it was not used ( P 5 .006). Interhospital variation in TBBx use when ROSE was used was signifi cant ( P , .001). Conclusions: TBBx was the only risk factor for complications during EBUS-TBNA procedures. ROSE signifi cantly reduced the use of TBBx.